Abstract
Rationale & Objective:
Simple kidney cysts are common and usually considered of limited clinical relevance. They are associated with older age and lower glomerular filtration rate (GFR), but little is known of their association with progressive chronic kidney disease (CKD) which was the focus of this study.
Study Design:
Observational cohort study.
Setting & Participants:
Patients with pre-surgical CT or MRI imaging who underwent a radical nephrectomy for a tumor. We reviewed the retained kidney images to characterize parenchymal cysts at least 5 mm in diameter according to size and location.
Exposures:
Parenchymal cysts at least 5 mm in diameter in the retained kidney. Cyst characteristics were correlated with microstructural findings on kidney histology.
Outcomes:
Progressive CKD defined by dialysis, kidney transplantation, a sustained ≥40% decline in eGFR, or an eGFR <10 ml/min/1.73m2 that was at least 5 ml/min/1.73m2 below the post-nephrectomy baseline for at least 3 months.
Analytical Approach:
Cox models assessed the risk of progressive CKD. Models adjusted for baseline age, sex, body mass index, hypertension, diabetes, eGFR, proteinuria, and tumor volume. Non-parametric Spearman’s correlations were used to examine the association of the number and size of the cysts with clinical characteristics, kidney function, and kidney volumes.
Results:
There were 1195 patients with 50 progressive CKD events over a median 4.4 years of follow-up. On baseline imaging, 37% had at least one cyst, 34% had at least one cortical cyst, and 8.3% had at least one medullary cyst. A higher number of cysts was associated with progressive CKD and was modestly correlated with larger nephrons and more nephrosclerosis on kidney histology. The number of medullary cysts was more strongly associated with progressive CKD than the number of cortical cysts.
Limitations:
Patients who undergo a radical nephrectomy may differ from the general population. A radical nephrectomy may accelerate the risk of progressive CKD. Genetic testing was not performed.
Conclusion:
Cysts in the kidney, particularly the medulla, should be further examined as a potentially useful imaging biomarker of progressive CKD beyond the current clinical evaluation of kidney function and common CKD risk factors.
Index words: Simple kidney cysts, chronic kidney disease, radical nephrectomy, medulla, kidney failure
Plain Language Summary
Kidney cysts are common and often considered of limited clinical relevance despite being associated with lower GFR. We studied a large cohort of patients who had a kidney removed due to a tumor to determine if cysts in the retained kidney were associated with kidney health in the future. We found that more cysts in the kidney and, in particular, cysts in the deepest tissue of the kidney (the medulla) were associated with progressive kidney disease including kidney failure where dialysis or a kidney transplantation is needed. Patients with cysts in the kidney medulla may benefit from closer monitoring.
Introduction
Simple kidney cysts are common and usually considered of limited clinical relevance. They have been consistently associated with older age and CKD. The reported prevalence of kidney cysts has been quite variable, mainly due to differences in imaging modalities. The prevalence of simple renal cysts is about 7.7% to 11.9% on ultrasonography.1–3 The prevalence is much higher at about 27% to 41% with computed tomography (CT) imaging due to higher spatial resolution.4,5 Contrast-enhanced CT can also differentiate between cortical and medullary cysts. The prevalence of cysts increases with older age and with a lower minimal cyst diameter. For ages 19–49 years, 39%, 22%, 7.9%, and 1.6% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter. For ages 50–75 years, 63%, 43%, 22%, and 7.8% had a cortical or medullary cyst ≥2, ≥5, ≥10, and ≥20 mm in diameter.6 Simple kidney cysts are also associated with reduced kidney function and CKD.7,8
An association between kidney cysts and renal cell carcinoma (particularly papillary) is well established.9,10 Patients with renal cell carcinoma who undergo a partial or complete nephrectomy are at increased risk for acute kidney injury and progressive CKD.11–15 In living kidney donors, kidney cysts associate with nephrosclerosis and larger tubules on a needle core kidney biopsy histology.16 Patients who undergo a radical nephrectomy for a tumor allow study of kidney microstructural pathology on large wedge sections of the removed kidney. Similar to kidney donors, tumor patients undergo a pre-nephrectomy contrast-enhanced CT or MRI that can detect small cysts and determine their location in the cortex versus medulla.17–19 Further, kidney tumor patients have more comorbidities than living kidney donors and are actively followed for progressive CKD outcomes.
A prior study found that among 65 patients who both underwent a nephrectomy and were followed in a nephrology clinic, the 20 with a renal cyst had a higher risk of progressive CKD than the 45 without a cyst.20 However, limitations of this study were the small sample size, lack of cyst details, and potential selection bias when limited to nephrology clinic follow-up. Thus, we performed a study using a large sample of patients who underwent a nephrectomy for a kidney tumor and who were followed with annual visits as part of a standardized post-nephrectomy clinical protocol. We assessed whether kidney cyst size, number, and location were associated with concurrent clinical characteristics, measures of nephron size or nephrosclerosis on kidney histology, and progressive CKD during follow-up.
Methods
Study populations
We studied patients who underwent a radical nephrectomy for a renal tumor between 2000 and 2019 at the Mayo Clinic in Rochester, Minnesota. This cohort is part of the Aging Kidney Anatomy study and was identified using the Mayo Clinic Nephrectomy Registry as previously described.21–23 Only patients with available electronic pre-nephrectomy CT or MRI imaging with no metastatic lesions or positive lymph nodes at the time of surgery and had no cancer recurrence or death at least 4 months after nephrectomy were studied. Our initial cohort included 1638 patients. After excluding patients without electronic imaging (N=202), kidney failure (dialysis or eGFR<10 ml/min/1.73 m2) within 4 months after nephrectomy (N=28), cancer recurrence or death within 4 months after nephrectomy (N=110), missing post-nephrectomy baseline serum creatinine (N=71), and 32 patients with a diffuse specific kidney disease observed on histology (including severe and diffuse tubulointerstitial inflammation, severe ischemia with %IFTA involving most of the cortex, a large focal scar, or end-stage kidney histology), our final cohort had 1195 patients that underwent further analysis. None of the patients in the final cohort were known to have any form of congenital/genetic polycystic kidney disease. The study was approved by the Mayo Clinic Institutional Review Board with a waiver of consent as data were limited to the medical record.
Clinical characteristics at baseline
The electronic medical records of tumor patients were reviewed to obtain clinical characteristics at the time of the nephrectomy. These included age, sex, race, height, weight, blood pressure, 24-hour urinary protein excretion, serum creatinine (corrected to standardized values if assayed before October 2006), and history of kidney stones, hypertension, or diabetes (based on review of perioperative medical record notes). Body mass index (BMI) was calculated from weight divided by height squared. The 24-hour urine protein excretion was estimated from a spot urine protein-osmolality ratio.24 Estimated glomerular filtration rate (eGFR) was calculated using the 2021 CKD-EPI equation.25 As the nephrectomy itself causes a decline in eGFR, we defined progressive CKD relative to the post-nephrectomy new baseline eGFR. To do this, we used the serum creatinine value closest to but before 4 months after the nephrectomy for baseline eGFR.22
Microstructures on kidney histology
The non-tumor parenchyma of the nephrectomy specimen was analyzed to characterize nephrosclerosis and nephron size with morphometry as previously described.22,23 Briefly, high resolution digital images of scanned PAS-stained wedge sections were magnified on a large tablet. Cortex, non-sclerosed glomeruli, globally sclerosed glomeruli (GSG), and interstitial fibrosis and tubular atrophy (IFTA) foci were manually traced by physician research fellows. All annotations were reviewed and corrected as needed by Dr. Denic who has extensive experience and training with annotating these microstructures. Weibel and Gomez stereology models were used to calculate non-sclerosed glomerular volume and glomerular density.26 The reciprocal of glomerular density calculated cortex volume per glomerulus as a direct correlate of nephron size.27 Percentage GSG was determined by dividing the number of GSG by the number of all glomeruli (non-sclerosed and sclerosed glomeruli). The area of IFTA divided by cortex area calculated %IFTA, and the number of individual IFTA foci divided by cortex area calculated IFTA foci density (per cm2). Arteriosclerosis was assessed by the average percentage luminal stenosis (from intimal thickening) using the three most orthogonal small to medium sized arteries on the wedge section. The percentage luminal stenosis was determined from the area of intima divided by the area of intima and lumen. Examples of these annotations and comparisons of clinical associations with morphometric measures of chronicity by research fellows to clinical associations with chronicity scores by renal pathologists’ visual inspection has been previously reported.22,28
Kidney cysts and other imaging characteristics
The pre-nephrectomy abdominal CT or MRI images in tumor patients were reviewed to determine the location, size, and diameter of kidney cysts in the retained kidney. Cysts were not studied in the removed kidney with the renal tumor. Renal cysts were defined as non-enhancing hypodense circular or near circular region with sharpy defined boundaries.29 There is underdetection of very small kidney cysts with certain patient characteristics (obesity) as well as imaging parameters that affect spatial resolution.6 Thus, we required a minimum threshold of at least 5 mm for the diameter for cysts to reduce bias from factors that affect cyst detection. Cortical versus medullary cyst location was determined by angiographic phase images or with a clear exophytic growth (Figure 1). If the cyst was at the cortical-medullary junction or was otherwise indeterminant between cortex and medulla, it was classified as cortical. This was based on analysis that showed that indeterminant cysts were more consistent in their clinical associations with cortical rather than medullary cysts (data not shown). Using axial images, maximum cyst diameter of the largest cyst (cortex or medulla) and the maximum medullary cyst diameter was determined. Parapelvic cysts were evaluated separately from cortical and medullary parenchymal cysts. A semi-automated image processing tool (ITK-SNAP software, version 2.2; University of Pennsylvania, Philadelphia, PA) was used to determine the kidney tumor volume of the removed kidney and the cortical and medullary volume of the retained kidney (excluding cysts) as previously reported.16
Figure 1.
Examples of renal cysts in different locations. Contrast-enhanced CT (corticomedullary phase) of the kidney in various reformats show A) an exophytic cortical cyst, B) an endophytic cortical cyst, and C) a cyst in the medulla (indicated by white arrows).
Outcomes
Per a standardized clinical protocol for long-term monitoring after the nephrectomy, patients returned for follow-up visit every 3–6 months during the first year and then every 6–12 months subsequently. This visit included a measurement of serum creatinine level. For patients who did not return for a follow-up visit, attempts were made to contact by phone and determine vital status. If alive, they were surveyed or had outside medical records reviewed for recent serum creatinine levels, dialysis, and kidney transplantation. Progressive CKD was defined by dialysis, kidney transplantation, a 40% or more decline in eGFR sustained for at least 3 months, or a eGFR below 10 ml/min/1.73m2 that was at least 5 ml/min/1.73m2 below baseline for at least 3 months. Medical records were reviewed to determine the cause of kidney failure (dialysis, kidney transplantation, or eGFR <10 ml/min/1.73m2. Follow-up ended on February 17, 2023.
Statistical analysis
The cyst counts in the cortex and medulla, the largest any cyst diameter, and the largest medullary cyst diameter were described. The risks of progressive CKD with these cyst measures were assessed using Cox proportional hazards models with censoring at the first occurrence of the last serum creatinine value, cancer recurrence, February 17, 2023, or death. These models were evaluated unadjusted, adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, baseline eGFR, proteinuria, and tumor volume), adjusted for measures of nephron size (glomerular volume and cortex per glomerulus), or adjusted for measures of nephrosclerosis (%global glomerulosclerosis, %IFTA, IFTA foci density, and %luminal stenosis). The risk of progressive CKD with largest cyst diameter was only assessed in persons with a cyst and the risk of progressive CKD with largest medullary cyst diameter was only assessed in persons with medullary cysts. Cumulative incidence plots (1 - Kaplan–Meier survival) graphically presented the risk of progressive CKD by cortical and medullary cyst counts. As a sensitivity analysis, a 30% rather than 40% decline in eGFR and an eGFR <15 ml/min/1.73m2 rather than <10 ml/min/1.73m2 were used in the definition of progressive CKD. Non-parametric Spearman’s correlations were used to compare number and size of the cysts with clinical characteristics, kidney function, kidney volumes. These correlations were then age- and sex-adjusted using partial Spearman correlations. Due to strong association with age and sex, age- and sex- adjusted partial Spearman correlations were used to correlate number and size of the cysts with measures of nephron size and nephrosclerosis. All analyses were performed using BlueSky Statistics Version 7.40, and R version 4.1.2. A p-value less than 0.05 was considered statistically significant.
Results
Clinical and cyst characteristics of cohort
The final study population included 1195 patients, after excluding patients without available CT/MRI images, patients who had transplant, dialysis, eGFR<10 ml/min/ 1.73m2, cancer recurrence within 4 months following nephrectomy, patients with missing serum creatinine data, and patients with specific kidney disease (Figure 2). There were 50 progressive CKD events over a median 4.4 years of follow-up, and none of these patients had polycystic kidney disease as a reported cause of their kidney disease during follow-up (Table S1). The specific 50 events were 8 dialysis, 1 kidney transplant, 15 sustained eGFR <10 ml/min/1.73 m2, and 26 sustained 40% decline in eGFR. Baseline patient characteristics are described in Table 1. A parenchymal cyst in the retained kidney was present in 37.7%, and if present, the mean diameter of the largest cyst was 2.0 cm. Men were more likely than women to have a cyst (age-adjusted OR=1.69, p<0.001), and if present, cysts were larger in men than women (4 mm larger after age adjustment, p=0.002). Parenchymal cyst presence and size increased with age (sex-adjusted p<0.001 and p=0.003, respectively) and Figure S1 shows the frequency of parenchymal cysts and largest cyst diameter by age and sex.
Figure 2.
Selection of study population.
Table 1.
Baseline characteristics of 1195 patients with renal tumor.
| Clinical Characteristics | All patients (N=1195) | Patients with medullary cyst (N=104) | Patients with cortical cyst and no medullary cyst (N=346) | Patients with no cysts (N=745) |
|---|---|---|---|---|
| Age, years | 64.3 (11.8) | 68.0 (11.8) | 68.2 (9.9) | 62.0 (12.1) |
| Male | 768 (64.3%) | 69 (66.3%) | 249 (72.0%) | 450 (60.4%) |
| Race | ||||
| American Indian/Alaskan Native | 12 (1.0%) | 3 (2.9%) | 1 (0.3%) | 8 (1.1%) |
| Asian | 4 (0.3%) | 0 (0.0%) | 0 (0.0%) | 4 (0.5%) |
| Black | 21 (1.8%) | 0 (0.0%) | 10 (2.9%) | 11 (1.5%) |
| White | 1115 (93.3%) | 96 (92.3%) | 325 (93.9%) | 694 (93.2%) |
| Unknown/Other | 43 (3.8%) | 5 (4.8%) | 10 (2.9%) | 28 (4.7%) |
| aHispanic ethnicity | 17 (1.5%) | 0 (0.0%) | 3 (0.9%) | 14 (1.9%) |
| BMI, kg/m2 | 30.8 (6.7) | 30.4 (6.7) | 31.1 (6.4) | 30.7 (6.8) |
| Hypertension | 825 (69.0%) | 78 (75.0%) | 255 (73.7%) | 492 (66.0%) |
| Diabetes mellitus | 171 (14.3%) | 12 (11.5%) | 64 (18.5%) | 95 (12.8%) |
| History of kidney stones | 134 (11.2%) | 14 (13.5%) | 48 (13.9%) | 72 (9.7%) |
| Kidney function | ||||
| Pre-nephrectomy eGFR, ml/min/1.73m2 | 72.7 (19.2) | 72.3 (17.5) | 70.8 (19.4) | 73.6 (19.3) |
| Post-nephrectomy baseline eGFR, ml/min/1.73m2 | 51.2 (14.1) | 50.0 (13.9) | 48.2 (13.9) | 52.7 (13.9) |
| b24hr urine protein excretion, mg | 162 [92, 322] | 178 [95, 325] | 174 [107, 311] | 156 [83, 330] |
| Imaging characteristics | ||||
| Patients with CT imaging | 1058 (88.5%) | 91 (87.5%) | 315 (91.0%) | 652 (87.5%) |
| Patients with MRI imaging | 137 (11.5%) | 13 (12.5%) | 31 (9.0%) | 93 (12.5%) |
| cKidney cortical volume, cm3 | 125.0 (36.9) | 124.4 (34.7) | 124.1 (37.1) | 125.5 (37.2) |
| cKidney medullary volume, cm3 | 48.6 (15.4) | 47.7 (15.5) | 50.3 (16.1) | 48.0 (15.1) |
| Tumor volume of removed kidney, cm3 | 155 [61, 406] | 116 [41, 310] | 148 [58, 387] | 166 [67, 448] |
| Any parapelvic cysts | 17 (1.4%) | 3 (2.9%) | 10 (2.9%) | 7 (0.9%) |
| Parenchymal cyst characteristics of retained kidney | ||||
| Any kidney parenchymal cyst | 450 (37.7%) | 104 (100.0%) | 346 (100.0%) | 0 (0.0%) |
| Any cortical cysts | 412 (34.5%) | 66 (63.5%) | 346 (100.0%) | 0 (0.0%) |
| Any medullary cysts | 104 (8.7%) | 104 (100.0%) | 0 (0.0%) | 0 (0.0%) |
| Number of parenchymal cysts | 0.9 (1.7) | 3.2 (2.5) | 2.1 (1.9) | 0.0 (0.0) |
| Number of cortical cysts | 0.8 (1.6) | 1.8 (2.3) | 2.1 (1.9) | 0.0 (0.0) |
| Number of medullary cysts | 0.1 (0.4) | 1.4 (0.7) | 0.0 (0.0) | 0.0 (0.0) |
| Number with ≥2 cortical cysts | 206 (17.2 %) | 38 (36.5%) | 168 (48.6%) | 0 (0.0%) |
| Number with ≥2 medullary cysts | 29 (2.4 %) | 29 (100.0%) | 0 (0.0%) | 0 (0.0%) |
| dLargest parenchymal cyst diameter, cm | 2.0 (1.6) | 1.8 (1.5) | 2.1 (1.6) | --- |
| eLargest medullary cyst diameter, cm | 1.1 (0.6) | 1.1 (0.6) | --- | --- |
| Baseline kidney histology measures | ||||
| Glomerular volume, mm3 | 0.0028 (0.0010) | 0.0028 (0.0011) | 0.0030 (0.0011) | 0.0028 (0.0010) |
| Cortex per glomerulus, mm3 | 0.074 (0.031) | 0.078 (0.035) | 0.079 (0.035) | 0.070 (0.027) |
| % GSG | 8.8 (8.9) | 11.5 (10.0) | 10.3 (9.1) | 7.8 (8.4) |
| % Luminal stenosis | 54.7 (15.5) | 57.6 (13.3) | 57.3 (14.9) | 53.1 (15.8) |
| % IFTA | 3.7 (7.3) | 3.2 (4.8) | 4.4 (7.5) | 3.4 (7.5) |
| IFTA foci density, per cm2 | 25.9 (21.3) | 24.5 (16.1) | 30.4 (21.5) | 24.0 (21.5) |
| Outcomes during follow-up | ||||
| Progressive CKD | 50 (4.2%) | 10 (9.6%) | 11 (3.2%) | 29 (3.9%) |
Data presented as Mean (SD), N (%), or Median [25%, 75%]. GSG = globally sclerotic glomeruli, IFTA = interstitial fibrosis and tubular atrophy. CKD = chronic kidney disease.
Ethnicity missing in 32 patients.
Urine protein data missing in 154 patients.
Cortex and medulla volumes available in 663 patients.
Sample size n=450.
Sample size n=104.
Risk of progressive CKD with cysts
In further analysis, Table 2 presents the risk of progressive CKD with parenchymal cysts in the retained kidney. The number of cysts and the number of just cortical cysts was associated with progressive CKD, but this was attenuated after adjustment for clinical characteristics, nephron size, or nephrosclerosis. The number of medullary cysts was more strongly associated with progressive CKD than was the number of cortical cysts. Unlike cortical cysts, the risk of progressive CKD with number of medullary cysts was not attenuated after adjustment for clinical characteristics, nephron size, or nephrosclerosis. Similar patterns for the association with progressive CKD were evident when number of cysts, number of cortical cysts, and number of medullary cysts were split into categories. Among 450 patients with any kidney cyst and among 104 patients with a medullary cyst, the largest cyst diameter or largest medullary cyst diameter were not associated with progressive CKD in unadjusted or adjusted analyses. Figure 3 shows the death censored incidence of progressive CKD with number of cortical cysts and medullary cysts. Presence of a parapelvic cyst did not associate with progressive CKD (unadjusted HR=0.86 [95% CI: 0.21–3.57], p=0.8). Patterns of association between parenchymal cysts and progressive CKD were similar using a 30% rather than 40% decline in eGFR and an eGFR <15 ml/min/1.73m2 rather than <10 ml/min/1.73m2 in the definition of progressive CKD (Table S2).
Table 2.
Risk of progressive CKD with parenchymal cyst characteristics of the retained kidney among 1195 patients who underwent a radical nephrectomy.
| Parenchymal cyst measurements | Unadjusted | Adjusted for CKD risk factors and kidney function* | Adjusted for nephron size on kidney histology** | Adjusted for nephrosclerosis on kidney histology*** | ||||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
| Number of cysts | 1.25 (1.13–1.38) | <0.001 | 1.17 (1.04–1.32) | 0.007 | 1.13 (1.00–1.26) | 0.04 | 1.18 (1.07–1.31) | 0.002 |
| Number of cortical cysts | 1.26 (1.12–1.42) | <0.001 | 1.15 (1.00–1.33) | 0.05 | 1.10 (0.96–1.27) | 0.2 | 1.18 (1.04–1.34) | 0.01 |
| Number of medullary cysts | 1.54 (1.16–2.06) | 0.004 | 1.64 (1.21–2.21) | 0.001 | 1.54 (1.15–2.07) | 0.004 | 1.61 (1.19–2.18) | 0.002 |
| Presence of 0 cysts | reference | reference | reference | reference | ||||
| Presence of 1 cyst | 0.53 (0.19–1.52) | 0.2 | 0.46 (0.16–1.34) | 0.2 | 0.41 (0.14–1.20) | 0.1 | 0.50 (0.18–1.44) | 0.2 |
| Presence of 2 cysts | 1.51 (0.63–3.64) | 0.4 | 1.33 (0.54–3.27) | 0.5 | 1.56 (0.64–3.76) | 0.3 | 1.36 (0.56–3.32) | 0.5 |
| Presence of ≥3 cysts | 2.35 (1.17–4.70) | 0.02 | 1.50 (0.70–3.21) | 0.3 | 1.23 (0.57–2.64) | 0.6 | 1.85 (0.91–3.78) | 0.09 |
| Presence of 0 cortical cysts | reference | reference | reference | reference | ||||
| Presence of 1 cortical cyst | 0.39 (0.12–1.27) | 0.1 | 0.32 (0.10–1.07) | 0.06 | 0.29 (0.08–0.97) | 0.04 | 0.37 (0.11–1.22) | 0.1 |
| Presence of 2 cortical cysts | 1.94 (0.81–4.65) | 0.1 | 1.65 (0.67–4.08) | 0.3 | 2.15 (0.89–5.18) | 0.09 | 1.70 (0.70–4.12) | 0.2 |
| Presence of ≥3 cortical cysts | 2.54 (1.24–5.19) | 0.01 | 1.44 (0.65–3.19) | 0.4 | 1.14 (0.50–2.56) | 0.8 | 1.85 (0.89–3.86) | 0.1 |
| Presence of 0 medullary cysts | reference | reference | reference | reference | ||||
| Presence of 1 medullary cyst | 1.49 (0.53–4.18) | 0.4 | 1.65 (0.58–4.67) | 0.4 | 1.45 (0.52–4.07) | 0.5 | 1.64 (0.58–4.63) | 0.4 |
| Presence of ≥2 medullary cysts | 3.97 (1.66–9.49) | 0.002 | 4.82 (1.96–11.84) | <0.001 | 3.84 (1.61–9.20) | 0.003 | 3.87 (1.60–9.36) | 0.003 |
| aLargest parenchymal cyst diameter per mm | 1.15 (0.91–1.45) | 0.3 | 1.04 (0.80–1.34) | 0.8 | 1.12 (0.87–1.44) | 0.4 | 1.14 (0.89–1.47) | 0.3 |
| bLargest medullary cyst diameter per mm | 0.54 (0.14–2.10) | 0.4 | 0.69 (0.16–2.94) | 0.6 | 0.62 (0.14–2.79) | 0.5 | 1.37 (0.26–7.38) | 0.7 |
CKD progression was defined as a sustained eGFR decline by 40% or <10 ml/min/1.73 m2 with at least a 5 ml/min/1.73 m2, dilaysis, or kidney transplantation. Sample size was 1195 patients with 50 CKD events. HR, hazard ratio; 95% CI, 95% confidence interval.
Adjusted for age, sex, BMI, hypertension, diabetes, eGFR, and proteinuria.
Adjusted for glomerular volume and cortex per glomerulus.
Adjusted for %glomerulosclerosis, %IFTA, IFTA density, and %luminal stenosis.
N=450 limited to patients who had any cyst (there were 21 CKD events in this subset).
N=104 limited to patients who had medullary cyst (there were 10 CKD events in this subset).
Figure 3. Risk of progressive CKD with number of cortical and medullary cysts.
Higher number of A) cortical cysts and B) medullary cysts were associated with progressive CKD (Log-rank p=0.004 for both).
Correlation of cysts with clinical and kidney histological characteristics
In Table 3 we have shown that number of cysts, number of cortical cysts, and diameter of largest cyst correlated with hypertension, lower eGFR, and proteinuria. However, most of these correlations were no longer evident after age and sex adjustment. Table 4 shows the age-sex-adjusted correlation of cyst characteristics with kidney histology microstructural findings. Number of cysts, number of cortical cysts, and diameter of largest cyst correlated with measures of nephron size and measures of nephrosclerosis (except arteriosclerosis as determined by % luminal stenosis). Number of medullary cysts only correlated with %GSG and this correlation was more modest than was number of cortical cysts with %GSG.
Table 3.
Spearman’s correlation of retained kidney parenchymal cyst characteristics with clinical and imaging characteristics among 1195 patients who underwent a radical nephrectomy.
| Number of parenhycmal cysts rs (p-value) | Number of cortical cysts rs (p-value) | Number of medullary cysts rs (p-value) | aLargest parenchymal cyst diameter rs (p-value) | bLargest medullary cyst diameter rs (p-value) | |
|---|---|---|---|---|---|
| Unadjusted | |||||
| Age | 0.26 (<0.001) | 0.26 (<0.001) | 0.09 (0.001) | 0.12 (0.01) | 0.04 (0.7) |
| Male | 0.11 (<0.001) | 0.12 (<0.001) | 0.01 (0.6) | 0.16 (<0.001) | 0.11 (0.3) |
| BMI | 0.01 (0.7) | 0.01 (0.7) | −0.02 (0.6) | −0.04 (0.4) | 0.10 (0.3) |
| Hypertension | 0.09 (0.002) | 0.10 (<0.001) | 0.04 (0.2) | −0.02 (0.7) | 0.02 (0.9) |
| Diabetes | 0.05 (0.07) | 0.07 (0.01) | −0.02 (0.4) | 0.01 (0.8) | −0.09 (0.4) |
| Pre-nephrectomy eGFR | −0.07 (0.02) | −0.07 (0.01) | 0.00 (0.9) | −0.09 (0.07) | 0.14 (0.2) |
| Proteinuria | 0.08 (0.009) | 0.10 (0.002) | 0.01 (0.7) | 0.12 (0.02) | 0.02 (0.9) |
| History of kidney stones | 0.07 (0.01) | 0.07 (0.02) | 0.02 (0.4) | 0.04 (0.4) | 0.09 (0.4) |
| Kidney cortical volume | −0.03 (0.4) | −0.03 (0.4) | −0.01 (0.9) | −0.10 (0.1) | 0.11 (0.4) |
| Kidney medullary volume | 0.04 (0.3) | 0.05 (0.2) | −0.03 (0.5) | −0.03 (0.6) | 0.18 (0.2) |
| Adjusted for age and sex | |||||
| BMI | 0.05 (0.1) | 0.05 (0.08) | 0.00 (0.9) | −0.01 (0.8) | 0.11 (0.3) |
| Hypertension | 0.01 (0.7) | 0.02 (0.5) | 0.01 (0.1) | −0.05 (0.3) | 0.00 (0.9) |
| Diabetes | 0.04 (0.2) | 0.06 (0.04) | −0.03 (0.3) | 0.00 (0.9) | −0.11 (0.3) |
| Pre-nephrectomy eGFR | 0.04 (0.2) | 0.04 (0.2) | 0.04 (0.2) | −0.05 (0.3) | 0.15 (0.1) |
| Proteinuria | 0.03 (0.4) | 0.04 (0.2) | 0.00 (0.9) | 0.08 (0.09) | 0.00 (0.9) |
| History of kidney stones | 0.07 (0.02) | 0.06 (0.05) | 0.02 (0.4) | 0.03 (0.5) | 0.09 (0.4) |
| Kidney cortical volume | 0.02 (0.5) | 0.01 (0.9) | 0.04 (0.3) | −0.13 (0.04) | 0.08 (0.5) |
| Kidney medullary volume | 0.06 (0.2) | 0.06 (0.2) | −0.01 (0.9) | −0.05 (0.5) | 0.17 (0.2) |
N=450 limited to patients who had any cyst.
N=104 limited to patients who had medullary cyst.
Table 4.
Age- and sex-adjusted partial Spearman’s correlations of retained kidney parenchymal cyst characteristics with kidney histology microstructural measures among 1195 patients who underwent a radical nephrectomy.
| Nephron size measures | Nephrosclerosis measures | |||||
|---|---|---|---|---|---|---|
| Glomerular volume rs (p-value) | Cortex per glomerulus rs (p-value) | %GSG rs (p-value) | IFTA density rs (p-value) | % IFTA rs (p-value) | %Luminal stenosis rs (p-value) | |
| Number of parenchymal cysts | 0.10 (<0.001) | 0.12 (<0.001) | 0.12 (<0.001) | 0.06 (0.03) | 0.07 (0.02) | 0.05 (0.06) |
| Number of cortical cysts | 0.12 (<0.001) | 0.13 (<0.001) | 0.12 (<0.001) | 0.09 (0.005) | 0.08 (0.005) | 0.05 (0.08) |
| Number of medullary cysts | 0.00 (0.9) | 0.02 (0.6) | 0.06 (0.05) | −0.04 (0.2) | −0.02 (0.5) | 0.02 (0.4) |
| aLargest parenchymal cyst diameter | 0.05 (0.3) | 0.09 (0.05) | 0.09 (0.05) | −0.01 (0.8) | 0.09 (0.06) | 0.08 (0.1) |
| bLargest medullary cyst diameter | 0.10 (0.3) | 0.03 (0.8) | 0.00 (0.9) | −0.16 (0.1) | −0.16 (0.1) | 0.04 (0.7) |
N=450 limited to patients who had any cyst
N=104 limited to patients who had medullary cyst
Discussion
Our study found an increased risk of progressive CKD with kidney cysts in the retained kidney among patients who undergo radical nephrectomy. An increased risk of progressive CKD was evident with cortical cysts, but this appears to be via the same pathways as lower eGFR, proteinuria, and common CKD risk factors (obesity, hypertension, and diabetes). The risk of progressive CKD was also attenuated when adjusting for larger nephron size and more nephrosclerosis on histology. There was a stronger risk of progressive CKD with medullary cysts than cortical cysts. Unlike cortical cysts, the risk of progressive CKD with medullary cysts showed no evidence of being via the same pathways as reduced eGFR, proteinuria, common CKD risk factors, larger nephron size, or nephrosclerosis.
Simple renal cysts are common, but the prognostic implications for CKD have been understudied. We found cortical cysts were more correlated with older age and male gender compared to medullary cysts, as was also seen in living kidney donors.6 In donors, medullary but not cortical cyst number and size associated with higher GFR and lower serum creatinine suggesting medullary cysts associate with hyperfiltration in this relatively healthy population.6 We did not find this to be evident in the current study of tumor patients. Rather, more cortical cysts were associated with lower eGFR, proteinuria, and CKD risk factors. Other studies have found renal cysts to associate with albuminuria in young adults.30 In our study, these correlations were no longer evident after age-sex-adjustment, except diabetes weakly correlated with number of parenchymal cortical cysts and history of kidney stones weakly correlated with number of parenchymal cysts. The biological basis for these correlations is uncertain. The risk of cysts with history of kidney stones may be related to obstructive nephropathy from past stones. Therefore, obstructive nephropathy could also be a potential cause for diverticula leading to cyst formation and growth.31
Our study showed that a higher number of cortical cysts and of any type of cysts associated with an increased risk of progressive CKD, consistent with a prior study in patients with kidney tumor.20 This risk was no longer evident after adjusting for kidney function and CKD risk factors. Another study found the presence of kidney cyst on ultrasound to be associated with onset of CKD but also not after adjusting for CKD risk factors.32 This suggests that evaluating the presence and number of any kidney cyst or cortical cyst does not meaningfully improve risk assessments for progressive CKD over standard clinical testing and evaluation. Further, these analyses suggest that presence of a few cortical cysts should not be considered an important independent prognostic factor for progressive CKD when considering a nephrectomy. However, this is not the case for medullary cysts. Patients with 2 or more medullary cysts are at about 4-fold higher risk of progressive CKD compared to patients without a medullary cyst. Among patients who developed progressive CKD during follow-up we found no evidence of any diagnosed polycystic kidney disease.
In kidney donors, glomerulosclerosis, IFTA, and larger tubules on kidney histology at the time of donation has been found to associate with presence of a kidney cyst.16 In this current study of tumor patients, glomerulosclerosis, IFTA, larger glomeruli and larger nephrons (cortex per glomerulus) correlated with more cortical cysts. Only glomerulosclerosis associated with higher number of medullary cysts. It is possible that cortical cysts are simply manifestations of CKD as evident by the chronic changes on histology. However, this is less clear with medullary cysts, which despite being more strongly associated with progressive CKD were only weakly correlated with glomerulosclerosis on histology. Thus, it is possible that medullary cysts represent either an early causal factor or a correlate of some early causal factor for CKD unlike cortical cysts which appear to be more of a manifestation of CKD. Some of these cysts, particularly those arising from the medulla, may have a genetic origin. A single COL4A3/4/5 mutation occurs in approximately 1% of the population and can cause kidney cysts.33 Some genes, such as ALG8, can cause multiple cysts but have a low penetrance level.34
There are underlying mechanisms for cysts formation and growth that may explain their association with CKD. Cysts arise from tubular diverticula35 and hyperfiltration may contribute to diverticular formation and growth. Renal ischaemia or injury prompts an aberrant hypertrophic response leading to cyst growth and leads to further nephron loss due to compensatory hyperfiltration.36,37 This pathway could explain the association of cortical cysts in particular with larger nephrons, nephrosclerosis, CKD, and CKD risk factors as seen in this study and a prior study in living kidney donors.16 Alternatively, medullary cysts have much less of an association with cortical nephrosclerosis and nephron size. Cortical cysts may tend to originate from the proximal tubule whereas medullary cysts originate from more distal segments of the nephron (as seen in autosomal dominant polycystic kidney disease). It is possible that medullary cysts, particularly if arising from collecting ducts, disrupt the function of more nephrons than do cortical cysts.
Our study had several limitations worth discussing. Our population was patients who underwent a radical nephrectomy for tumor and findings may differ in the two-kidney general population. A radical nephrectomy may accelerate the risk of progressive CKD due to hyperfiltration in the remaining kidney and this may potentially interact with pathways of kidney cyst formation. Nonetheless, tumor patients provide access to baseline contrast-enhanced kidney imaging to distinguish cortical from medullary cysts and to large wedge sections of kidney parenchyma for clearly defining parenchymal pathology. We could not reliably detect and study cysts smaller than 5 mm. With advances in imaging technology and protocols that obtain higher spatial resolution images, this may be possible. We classified indeterminate cysts near the corticomedullary junction as cortical cysts, and it is possible some of these indeterminate cysts may have been medullary cyst. Nonetheless, we wanted certainty in the detection of medullary cysts as they were more prognostic for progressive CKD than cortical cysts. Our study cohort was predominantly White and finding may differ in other race/ethnic groups. Proteinuria was estimated from protein to osmolality ratios as protein to creatinine ratios or actual 24h urine protein collections are not routinely obtained in this patient population. Genetic testing was not performed, and it is possible that there was a monogenetic cause of cysts in at least some patients in this cohort.
In conclusion, the detection, and number of cysts in the kidney, and in particular the medulla, may be useful imaging biomarker beyond current clinical evaluations for factors associated with progression of CKD and kidney failure. Further studies are needed to evaluate and confirm these findings in other populations and examine the predictive value of radiologically evaluating cysts for the purpose of refining assessments of the risk of progressive kidney disease.
Supplementary Material
Figure S1. Frequency of a detected cyst and largest cyst diameter among patients with cysts by age group in men and in women.
Table S1. Attributed primary cause of the progressive CKD in 50 patients based on medical record review.
Table S2. Risk of progressive CKD with cyst characteristics of the retained kidney among 1187 patients who underwent a radical nephrectomy.
Support:
This study was supported with funding from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358). The funder had no role in the study design, data collection, analysis, reporting, or the decision to submit for publication.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Financial Disclosure: The authors declare that they have no relevant financial interests.
References:
- 1.Ozveren B, Onganer E, Turkeri LN. Simple Renal Cysts: Prevalence, Associated Risk Factors and Follow-Up in a Health Screening Cohort. Urol J Mar 5 2016;13(1):2569–75. [PubMed] [Google Scholar]
- 2.Chang CC, Kuo JY, Chan WL, Chen KK, Chang LS. Prevalence and clinical characteristics of simple renal cyst. J Chin Med Assoc. Nov 2007;70(11):486–91. doi: 10.1016/S1726-4901(08)70046-7 [DOI] [PubMed] [Google Scholar]
- 3.Terada N, Arai Y, Kinukawa N, Terai A. The 10-year natural history of simple renal cysts. Urology. Jan 2008;71(1):7–11; discussion 11–2. doi: 10.1016/j.urology.2007.07.075 [DOI] [PubMed] [Google Scholar]
- 4.Tada S, Yamagishi J, Kobayashi H, Hata Y, Kobari T. The incidence of simple renal cyst by computed tomography. Clinical radiology. Jul 1983;34(4):437–9. [DOI] [PubMed] [Google Scholar]
- 5.Carrim ZI, Murchison JT. The prevalence of simple renal and hepatic cysts detected by spiral computed tomography. Clinical radiology. Aug 2003;58(8):626–9. [DOI] [PubMed] [Google Scholar]
- 6.Rule AD, Sasiwimonphan K, Lieske JC, Keddis MT, Torres VE, Vrtiska TJ. Characteristics of renal cystic and solid lesions based on contrast-enhanced computed tomography of potential kidney donors. Am J Kidney Dis. May 2012;59(5):611–8. doi: 10.1053/j.ajkd.2011.12.022 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Al-Said J, Brumback MA, Moghazi S, Baumgarten DA, O’Neill WC. Reduced renal function in patients with simple renal cysts. Kidney Int. Jun 2004;65(6):2303–8. [DOI] [PubMed] [Google Scholar]
- 8.Al-Said J, O’Neill WC. Reduced kidney size in patients with simple renal cysts. Kidney Int. Sep 2003;64(3):1059–64. doi: 10.1046/j.1523-1755.2003.00193.x [DOI] [PubMed] [Google Scholar]
- 9.Hayakawa M, Hatano T, Tsuji A, Nakajima F, Ogawa Y. Patients with renal cysts associated with renal cell carcinoma and the clinical implications of cyst puncture: a study of 223 cases. Urology. May 1996;47(5):643–6. doi: 10.1016/s0090-4295(96)00016-7 [DOI] [PubMed] [Google Scholar]
- 10.Visapaa H, Glucker E, Haukka J, Taari K, Nisen H. Papillary renal cell cancer is strongly associated with simple renal cysts. Urol Int. 2013;91(3):269–72. doi: 10.1159/000351751 [DOI] [PubMed] [Google Scholar]
- 11.Sun M, Bianchi M, Hansen J, et al. Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis. Eur Urol. Oct 2012;62(4):696–703. doi: 10.1016/j.eururo.2012.03.051 [DOI] [PubMed] [Google Scholar]
- 12.Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol. Sep 2006;7(9):735–40. doi: 10.1016/S1470-2045(06)70803-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Jeon HG, Jeong IG, Lee JW, Lee SE, Lee E. Prognostic factors for chronic kidney disease after curative surgery in patients with small renal tumors. Urology. Nov 2009;74(5):1064–8. doi: 10.1016/j.urology.2009.05.090 [DOI] [PubMed] [Google Scholar]
- 14.Cho A, Lee JE, Kwon GY, et al. Post-operative acute kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy. Nephrol Dial Transplant. Nov 2011;26(11):3496–501. doi: 10.1093/ndt/gfr094 [DOI] [PubMed] [Google Scholar]
- 15.Clark MA, Shikanov S, Raman JD, et al. Chronic kidney disease before and after partial nephrectomy. J Urol. Jan 2011;185(1):43–8. doi: 10.1016/j.juro.2010.09.019 [DOI] [PubMed] [Google Scholar]
- 16.Denic A, Alexander MP, Kaushik V, et al. Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults. Am J Kidney Dis. Jul 2016;68(1):58–67. doi: 10.1053/j.ajkd.2015.12.029 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Helenon O, Crosnier A, Verkarre V, Merran S, Mejean A, Correas JM. Simple and complex renal cysts in adults: Classification system for renal cystic masses. Diagn Interv Imaging. Apr 2018;99(4):189–218. doi: 10.1016/j.diii.2017.10.005 [DOI] [PubMed] [Google Scholar]
- 18.Adey GS, Pedrosa I, Rofsky NM, Sanda MG, DeWolf WC. Lower limits of detection using magnetic resonance imaging for solid components in cystic renal neoplasms. Urology. Jan 2008;71(1):47–51. doi: 10.1016/j.urology.2007.09.016 [DOI] [PubMed] [Google Scholar]
- 19.Krishna S, Leckie A, Kielar A, Hartman R, Khandelwal A. Imaging of Renal Cancer. Semin Ultrasound CT MR. Apr 2020;41(2):152–169. doi: 10.1053/j.sult.2019.12.004 [DOI] [PubMed] [Google Scholar]
- 20.Tatar E, Ozay E, Atakaya M, et al. Simple renal cysts in the solitary kidney: Are they innocent in adult patients? Nephrology (Carlton). May 2017;22(5):361–365. doi: 10.1111/nep.12778 [DOI] [PubMed] [Google Scholar]
- 21.Denic A, Ricaurte L, Lopez CL, et al. Glomerular Volume and Glomerulosclerosis at Different Depths within the Human Kidney. J Am Soc Nephrol. Aug 2019;30(8):1471–1480. doi: 10.1681/ASN.2019020183 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Denic A, Elsherbiny H, Mullan AF, et al. Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function. J Am Soc Nephrol. Nov 2020;31(11):2642–2652. doi: 10.1681/ASN.2020040449 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ricaurte Archila L, Denic A, Mullan AF, et al. A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor. J Am Soc Nephrol. Oct 2021;32(10):2623–2633. doi: 10.1681/ASN.2021020267 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Wilson DM, Anderson RL. Protein-Osmolality Ratio for the Quantitative Assessment of Proteinuria from a Random Urinalysis Sample. American Journal of Clinical Pathology. Oct 1993;100(4):419–424. doi:DOI 10.1093/ajcp/100.4.419 [DOI] [PubMed] [Google Scholar]
- 25.Inker LA EN, Coresh J, Tighiouart H, Wang D, Sang Y, Crews DC, Doria A, Estrella MM, Froissart M, Grams ME, Greene T, Grubb A, Gudnason V, Gutiérrez OM, Kalil R, Karger AB, Mauer M, Navis G, Nelson RG, Poggio ED, Rodby R, Rossing P, Rule AD,. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021; [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Weibel ER, Gomez DM. A principle for counting tissue structures on random sections. J Appl Physiol. Mar 1962;17:343–8. doi: 10.1152/jappl.1962.17.2.343 [DOI] [PubMed] [Google Scholar]
- 27.Denic A, Rule AD. Authors’ Reply. J Am Soc Nephrol. Feb 2021;32(2):517–518. doi: 10.1681/ASN.2020111615 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Denic A, Bogojevic M, Mullan AF, et al. Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies. J Am Soc Nephrol. Aug 3 2022;doi: 10.1681/ASN.2022030234 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Patel NS, Poder L, Wang ZJ, et al. The characterization of small hypoattenuating renal masses on contrast-enhanced CT. Clinical imaging. Jul-Aug 2009;33(4):295–300. doi: 10.1016/j.clinimag.2008.12.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Boo HJ, Lee JE, Chung SM, et al. The presence of simple renal cysts is associated with an increased risk of albuminuria in young adults. Korean J Intern Med. Mar 2022;37(2):425-+. doi: 10.3904/kjim.2020.576 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Baert L, Steg A. Is the diverticulum of the distal and collecting tubules a preliminary stage of the simple cyst in the adult? J Urol. Nov 1977;118(5):707–10. [DOI] [PubMed] [Google Scholar]
- 32.Chen J, Ma XJ, Xu DM, Cao W, Kong XL. Association between simple renal cyst and kidney damage in a Chinese cohort study. Renal failure. 2019;41(1):600–606. doi: 10.1080/0886022x.2019.1632718 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Gulati A, Sevillano AM, Praga M, et al. Collagen IV Gene Mutations in Adults With Bilateral Renal Cysts and CKD. Kidney Int Rep. Jan 2020;5(1):103–108. doi: 10.1016/j.ekir.2019.09.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Apple B, Sartori G, Moore B, et al. Individuals heterozygous for ALG8 protein-truncating variants are at increased risk of a mild cystic kidney disease. Kidney Int. Mar 2023;103(3):607–615. doi: 10.1016/j.kint.2022.11.025 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Darmady EM, Offer J, Woodhouse MA. The parameters of the ageing kidney. J Pathol. Mar 1973;109(3):195–207. [DOI] [PubMed] [Google Scholar]
- 36.Richard Johnson JF, Floege Jurgen, Tonelli Marcello. Comprehensive Clinical Nephrology. 2018;(6th Edition) [Google Scholar]
- 37.Grantham JJ. Acquired cystic kidney disease. Kidney Int. Jul 1991;40(1):143–52. doi: 10.1038/ki.1991.192 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. Frequency of a detected cyst and largest cyst diameter among patients with cysts by age group in men and in women.
Table S1. Attributed primary cause of the progressive CKD in 50 patients based on medical record review.
Table S2. Risk of progressive CKD with cyst characteristics of the retained kidney among 1187 patients who underwent a radical nephrectomy.