Autosomal Dominant Polycystic Kidney Disease Patients Requiring Nephrectomy: Characteristics and Surgical Considerations

ABSTRACT

Background

Nephrectomies are major surgeries often required in ADPKD for symptom control, removal of septic/malignant foci, and to create space for renal transplantation. Whether ADPKD patients should proceed with nephrectomy/ies should be guided by patient characteristics, technical considerations and anticipated risks and benefits.

Methods

A retrospective review of prospectively collected data for all patients who underwent nephrectomy/ies between 1 January 1995 and 31 December 2021, comparing ADPKD patients to patients with alternative primary nephrological conditions. Patient characteristics, technical aspects, and outcomes informing the risks and benefits of nephrectomies were examined. Statistical analyses included descriptive statistics, χ ²/Fisher's exact test and independent samples Mann–Whitney U test, as appropriate.

Results

At the time of first nephrectomy, ADPKD patients were older and more likely to have end‐stage renal failure, hypertension, gastro‐oesophageal reflux disease, and hernia compared to non‐ADPKD patients. They were more likely to require bilateral nephrectomies, open nephrectomies, and, where transplanted, receive donation after circulatory death. They were at higher risk of post‐operative hypotension, anaemia, and more likely to require blood transfusions. Otherwise, nephrectomies achieved their indications in our ADPKD cohort with no apparent increase in adverse events. Renal cell carcinoma appears to be of higher incidence in our cohort, with a high proportion of multifocality and bilaterality, advanced staging at diagnosis and incidental diagnoses on histopathology.

Conclusion

Overall, in our ADPKD patients who received nephrectomy/ies, the procedure appeared to be safe and effective, with benefits outweighing risks. RCC exclusion is a prudent consideration especially for ADPKD patients on dialysis awaiting transplantation.

Abbreviations

ADPKD

autosomal dominant polycystic kidney disease

AVF

arteriovenous fistula

CT

computed tomography

ESRF

end‐stage renal failure

GORD

gastro‐oesophageal reflux disease

IVC

inferior vena cava

MRI

magnetic resonance imaging

RCC

renal cell carcinoma

1. Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is characterised by the presence of renal cysts that grow over time, leading to enlarged kidneys, acute and chronic pain, infections, cystic rupture and haemorrhage, and a potentially higher risk of renal cell carcinoma (RCC), the latter with an earlier age of onset and potential for multifocal involvement [1, 2]. This means ADPKD patients often require nephrectomy/ies for symptom control, removal of septic/malignant foci, and to create space for renal transplantation.

While nephrectomies may provide these benefits for ADPKD patients, they are major surgeries and may have associated risks for mortality and morbidity. We aimed to examine the patient characteristics, surgical/technical aspects and outcomes informing the risks and benefits of this major surgery in ADPKD, in addition to developing an evidence‐based framework with important considerations to help support decision making for patients, nephrologists and surgeons, as well as peri‐operative management when proceeding with elective nephrectomy/ies.

2. Methods

This study is a retrospective review of prospectively collected clinical data for all patients who underwent nephrectomy/ies between 1 January 1995 and 31 December 2021 at Central and Northern Adelaide Renal and Transplantation Services (CNARTS), the statewide transplantation centre in South Australia that provides renal and transplantation services (including nephrectomies) for patients aged 18 and above from South Australia (and from another state or territory in Australia under certain circumstances).

2.1. Patient Cohort

We compared ADPKD patients who required nephrectomy/ies to patients without ADPKD who had alternative primary nephrological conditions and required the same procedure (designated non‐ADPKD hereon). The use of patients who proceeded with nephrectomy/ies was an important consideration for several reasons. Firstly, this cohort is likely to provide the most accurate estimation of the prevalence of RCC lesion(s) in ADPKD, as it is possible that these lesion(s) may not be detected on radiological studies alone. Our findings are compared to published literature on RCC in ADPKD based on histopathological diagnosis. The comparison of ADPKD patients to non‐ADPKD patients with an alternative primary nephrological diagnosis also aimed to reduce the discrepancy in renal function and the need for renal replacement therapy, as renal function and mode of renal replacement therapy could both contribute to the development of RCC. To improve readability and focus, we also report in two separate papers on two other extrarenal manifestations of ADPKD: thromboembolic events and intracranial aneurysms [3, 4]. ADPKD patients were previously found to be at a higher risk of thromboembolic events post‐transplantation [5], compared to patients with other primary nephrological conditions. Our use of this patient cohort provides an opportunity to examine this extrarenal manifestation outside a dedicated transplantation setting, and allows for examination of the temporal relationship between thromboembolic event(s) and the timing of nephrectomy/ies and/or renal transplantation. On the other hand, major elective surgeries, including nephrectomies, pose risks for aneurysmal rupture, but also present opportunities for ADPKD patients to undergo screening for undiagnosed intracranial aneurysms, thus informing the risks of surgery and prompting appropriate perioperative management. The use of this patient cohort is likely to be representative of ADPKD patients requiring major surgeries.

2.2. Clinical Data

At CNARTS, patient and procedure details were prospectively entered into a surgical database. Medical progress notes and discharge summaries were prospectively written by medical officers during each hospitalisation. All inpatient and outpatient clinical encounters, discharge summaries and investigations, including pathology and imaging reports, are linked to an electronic medical record.

For this study, details were extracted from the surgical database for all patients who underwent nephrectomy/ies during the specified timeframe. Discharge summaries and other clinical records, including histopathology and imaging records, were reviewed for all patients up to and including 31 December 2021, extracting further information on patient demographics, primary nephrological diagnosis, other co‐morbidities, indication(s) for nephrectomy, age and renal function at the time of nephrectomy, mode of renal replacement therapy (dichotomised to dialysis or transplantation), incidents of mass effect, renal malignancy, thromboembolic events, intracranial aneurysms and outcomes of nephrectomy (length of admission; resolution of symptoms; post‐operative hypotension, anaemia, arteriovenous fistula thrombosis, requirement for intensive care/inotropic support, blood transfusion, unplanned dialysis; return to theatre; infective complications; need for post‐operative rehabilitation; mortality and any other complications).

Diagnosis of ADPKD is made by treating nephrologists when there is radiological confirmation of kidney cysts according to current diagnostic criteria [6, 7]; genetic analysis for ADPKD is not routinely carried out at present. Simultaneous/synchronous procedures were defined as procedures undertaken during the same operative session, whereas staged/asynchronous procedures refer to procedures undertaken at two separate time points.

2.3. Statistical Analyses

Descriptive statistics are presented for all patients and for each group. The prevalence of each demographic characteristic or outcome measure is presented as an absolute number and percentage and evaluated using the χ ²/Fisher's exact test, as appropriate. Stage of chronic kidney disease at first nephrectomy is presented as a median and interquartile range; length of admission is presented as a mean with standard deviation. Age at first nephrectomy and at follow up are presented as a mean with standard deviation and mean rank, the latter evaluated using independent samples Mann–Whitney U test to avoid the assumption that data is normally distributed. In general, p‐values < 0.05 were considered statistically significant. Statistical analyses were undertaken using the software IBM SPSS Statistics (v28.0.0.0).

3. Results

3.1. Patient Characteristics

During this 26‐year period, 115 nephrectomies were performed on 84 patients at CNARTS (Figure 1). Fifty two of these patients had ADPKD; none received tolvaptan. Thirty two patients had another primary nephrological diagnosis, including glomerulonephritidies (n = 10), obstructive nephropathy (n = 9), recurrent pyelonephritis (n = 4), renal artery stenosis/aneurysm (n = 4), diabetic nephropathy (n = 2), analgesic nephropathy (n = 1) and other (n = 2). There were no statistically significant differences for gender or age at follow up between the ADPKD and non‐ADPKD groups, but our ADPKD patients were older at the time of first nephrectomy [3]. They were also more likely to have end‐stage renal failure (ESRF) with a pre‐existing requirement for renal replacement therapy, hypertension, gastro‐oesophageal reflux disease (GORD) and hernia (Table 1).

FIGURE 1.

84 individual patients who underwent 115 nephrectomies at Central and Northern Adelaide Renal and Transplantation Services (CNARTS) were identified from 96 operative records between 1995 and 2021. N = number of kidneys removed.

TABLE 1.

Demographics of patients in the ADPKD and non‐ADPKD groups.

Parameter	ADPKD	Non‐ADPKD	p
	n = 52	n = 32
Gender, n (%)
Male	37 (71.2)	20 (62.5)	0.410
Female	15 (28.8)	12 (37.5)
Age at follow up (years)
Mean ± SD	61.74 ± 11.07	59.36 ± 13.42
Mean rank	38.82	36.63	0.673
Age at first nephrectomy (years)
Mean ± SD	53.33 ± 9.275	44.69 ± 14.44
Mean rank	46.05	33.27	0.017
CKD class at first nephrectomy, median (IQR)	5 (5, 5)	4 (2, 5)	< 0.001
Unilateral nephrectomy only	25 (48.1)	24 (75.0)	0. 041
Bilateral nephrectomy required	27 (51.9)	8 (25.0)
Simultaneous nephrectomies	17 (32.7)	2 (6.3)	0.105
Staged bilateral nephrectomies	10 (19.2) a	6 (15.6) a
Co‐morbidities, n (%)
Hypertension	45 (86.5)	10 (31.2)	< 0.001
Hypercholesterolaemia	15 (28.8)	3 (9.3)	0.054
Gastro‐oesophageal reflux disease	10 (19.2)	0 (0)	0.011
Hernia	9 (17.3)	0 (0)	0.012
Anaemia	9 (17.3)	1 (3.1)	0.081
Type 2 diabetes mellitus	6 (11.5)	3 (9.3)	1.000
Gout	5 (9.6)	0 (0)	0.151
Depression	4 (7.7)	0 (0)	0.293
Ischaemic heart disease	4 (7.7)	1 (3.1)	0.645
Obesity	3 (5.8)	0 (0)	0.284
Osteoporosis	3 (5.8)	0 (0)	0.284
Osteoarthritis	3 (5.8)	0 (0)	0.284
Atrial fibrillation	3 (5.8)	0 (0)	0.284
Thyroid conditions	2 (3.8)	0 (0)	0.523
Diverticular disease	2 (3.8)	0 (0)	0.523
Obstructive sleep apnoea	1 (1.9)	1 (3.1)	1.000
Cigarette smoking	9 (17.3)	9 (28.1)	0.280
Other	16	7

Note: Bold values are statistically significant.

^a Two patients in the ADPKD group and one patient in the control group had their initial nephrectomy at another centre, and their subsequent contralateral nephrectomy at CNARTS. The surgical approach and indications for their initial nephrectomies undertaken elsewhere were not included in subsequent analyses.

In patients requiring renal replacement therapy, the proportion of patients managed with dialysis or transplantation was similar for both groups. Among patients who had received renal transplantation at the time of follow up (n = 44 in the ADPKD group and n = 21 in the non‐ADPKD group), there were no significant gender differences. Donation after death predominated in both groups (28/44 in ADPKD, 63.6%; 16/21 in non‐ADPKD, 76.1%; p‐value = 0.5), but donation after circulatory death was higher in ADPKD (20 patients received transplant grafts donated after brain death, eight received transplant grafts donated after circulatory death; all 16 non‐ADPKD patients received transplant grafts donated after brain death; p‐value = 0.03).

3.2. Surgical Considerations

ADPKD patients were more likely to require bilateral nephrectomies and/or open nephrectomies (Tables 1 and 2). Following the introduction of laparoscopic polycystic nephrectomy at our centre, most ADPKD patients continued to receive open nephrectomies (69% nephrectomies since the first laparoscopic procedure) and the overall proportion of laparoscopic procedures remained steady over time in this particular patient cohort.

TABLE 2.

Surgical approach for nephrectomy by patient groups.

Parameter	ADPKD	Non‐ADPKD	p
	n = 77	n = 38
Surgical approach, n (%)
Open nephrectomy	61 (79.2)	10 (26.3)	< 0.001
Laparoscopic transperitoneal	16 (20.8)	23 (60.5)
Laparoscopic retroperitoneal	0 (0)	3 (7.8)
Laparoscopic converted to open	0 (0)	2 (5.2)
Side of nephrectomy, n (%) a
Left nephrectomy	38	23	0.355
Right nephrectomy	39	15

Note: Bold values are statistically significant.

^a Does not include three left nephrectomies undertaken at another centre prior to these patients undergoing a right nephrectomy at CNARTS.

Most polycystic nephrectomies were undertaken to create space for transplantation grafts (n = 42) as most of our ADPKD patients had enlarged kidneys which caused mass effect: displacement and compression of their major blood vessels, stomach (Figure 2a) and/or small/large bowel (Figure 2b; none suffered bowel obstructions), as well as solid organs such as the liver, spleen, pancreas; though most did not cause significant symptoms. A small number of nephrectomies (n = 4) were indicated to relieve significant consequences of the mass effect. Recurrent major blood vessel compression and deep vein thromboses were described previously in one of these patients [8], and another patient received bilateral nephrectomies for recurrent mass effect on his renal transplantation grafts causing obstructive uropathy (Figure 2c upper panel), and symptomatic contralateral inguinal hernia. Other indications for nephrectomy/ies in ADPKD were cystic haemorrhage or pain (n = 16), colonisation or recurrent infection (n = 12), and radiologically diagnosed malignancy (n = 2).

FIGURE 2.

Mass effect from enlarged polycystic kidneys can cause compression on both solid and hollow organs. (a) Coronal and axial views of one ADPKD patient's computed tomography whose enlarged left kidney(14 × 15 cm) compressed on his distal gastric body and antrum, causing decreased appetite and weight loss. (b) Coronal and sagittal views of one ADPKD patient's computed tomography, showing compression and displacement of her small and large intestines but without causing bowel obstruction. (c) Computed tomography showing a patient's native polycystic kidney compressing on his renal transplantation graft in the right iliac fossa (upper panel) and another patient's very enlarged liver cyst (lower panel).

Nephrectomy/ies were undertaken in non‐ADPKD patients to remove focus/i of malignancy (n = 11) or sepsis (n = 7), for hypertension refractory to medical management (n = 7), structural issues (n = 7), renal infarction (n = 2), etc.

3.3. Outcomes of Nephrectomies

The purpose/indication for nephrectomy/ies was achieved in all but two patients (one ADPKD and one non‐ADPKD), both of whom required staged bilateral nephrectomies for source control of recurrent urinary tract infections. Staged bilateral nephrectomies in all other ADPKD patients were for differing indications, e.g., initial nephrectomy for cystic haemorrhage/pain, subsequent contralateral nephrectomy for infection.

Table 3 summarises the remaining outcome measures for each admission for nephrectomy/ies. Of note, post‐operative hypotension, anaemia, and requirements for packed red blood cell transfusion and intensive care admission were significantly higher among ADPKD patients compared to non‐ADPKD patients. There was no statistically significant difference in the incidence of post‐operative hypotension when stratified by the number of kidneys removed during the same procedure and the surgical approach (Table 4). Three patients who underwent staged bilateral nephrectomy sustained post‐operative hypotension after one of their nephrectomies: one following their first nephrectomy and two following their latter nephrectomy.

TABLE 3.

Outcomes of each admission for nephrectomy/ies by patient groups.

Parameter, n (%)	ADPKD	Non‐ADPKD	p
	n = 60	n = 36
Length of admission in days, mean ± SD	7.0 ± 3.5	6.0 ± 4.2	0.250
Admission to intensive care unit	13 (21.6)	4 (11.1)	0.297
Inotropic support	7	1
Respiratory support	0	1
Monitoring only	6	2
Post‐operative hypotension	12 (20.0)	1 (2.7)	0. 016
Post‐operative anaemia	19 (31.6)	1 (2.7)	0. 0007
Requirement for packed red blood cell transfusion	18 (30.0)	2 (5.5)	0. 004
Arteriovenous fistula thrombosis	3 (5.0)	0 (0.0)	0.289
Post‐operative hyperkalaemia	11 (18.3)	4 (11.1)	0.345
Unplanned dialysis	6 (10.0)	1 (2.7)	0.187
Return to theatre	4 (6.7)	1 (2.7)	0.406
Infection
Surgical wound	4 (6.7)	0 (0.0)	0.289
Urinary tract	0 (0.0)	1 (2.7)	0.375
Hospital acquired pneumonia	5 (8.3)	0 (0.0)	0.153
Inpatient rehabilitation	1 (1.6)	0 (0.0)	0.542
Mortality
Immediate	0	0
1‐year post operatively	2 (3.3)	1 (2.7)	0.879

Note: Bold values are statistically significant.

TABLE 4.

ADPKD patients who sustained hypotension post nephrectomy, stratified by number of kidney(s) removed and surgical approach.

Parameter, n	Post‐operative hypotension		p
	Yes	No
	n = 12	n = 48
Number of kidney removed
One (unilateral nephrectomy and staged bilateral nephrectomies)	11	32	0.085
Two (simultaneous bilateral nephrectomies)	1	16
Surgical approach
Open nephrectomy	7	38	0.136
Laparoscopic transperitoneal	5	10

No patients died in the immediate post‐operative period, but two ADPKD patients and one non‐ADPKD patient died within 1 year of their nephrectomy/ies. One ADPKD patient died of an aneurysmal rupture 8 months after bilateral nephrectomies, as described separately [4]. Another ADPKD patient died from a flare of a pre‐existing psychiatric condition, which was stable at the time of nephrectomy. The non‐ADPKD patient had reflux nephropathy and a functioning allograft at the time of his nephrectomies, and underwent removal of both kidneys with the whole length of both ureters, following recurrent urinary tract infections and ascending infection with pyelonephritis, including episodes caused by multi‐resistant Streptococcus and Pseudomonas spp. His left nephrectomy was complicated by residual collection in the left renal bed, possibly an infected hematoma, which was drained. Unfortunately, despite his nephrectomies and collection drainage, he continued to contract urinary tract infections, and ultimately died from Pseudomonal urosepsis.

One ADPKD patient required inpatient rehabilitation following her admission. This was a premorbidly independent 59‐year‐old female who was electively admitted for simultaneous bilateral native polycystic nephrectomies, failed allograft nephrectomy and abdominoplasty. Her post‐operative course was complicated by hospital‐acquired pneumonia, antibiotic‐related diarrhoea, anaemia and adrenal insufficiency diagnosed via short synacthen test, despite sparing of her adrenal glands intra‐operatively, initially requiring admission to the intensive care unit for inotropic support. Her length of stay was 13 days acutely and 8 days at a rehabilitation facility. Following her discharge from rehabilitation, she developed abdominal wall abscesses requiring readmission and surgical drainage.

Return to theatre was required for four ADPKD patients and one non‐ADPKD patient. Three ADPKD patients required return to theatre for surgical wound infection, whereas the other ADPKD patient and non‐ADPKD patient were returned to theatre to control post‐operative bleeding.

The average length of admission for all nephrectomies was 7 ± 4 days and was comparable between the ADPKD and non‐ADPKD groups. Across both groups, patients who received staged bilateral nephrectomies had a higher cumulative length of admission (Table 5) but there were no significant differences detected in other outcomes.

TABLE 5.

Length of admission by approach of nephrectomy and patient groups.

	Staged bilateral nephrectomies	Simultaneous bilateral nephrectomies + unilateral nephrectomy only	p	Simultaneous bilateral nephrectomies	p	Unilateral nephrectomy only	p
ADPKD	14.5 ± 6.0	6.9 ± 3.5	< 0.001	7.0 ± 2.6	< 0.001	6.8 ± 4.1	< 0.001
Non‐ADPKD	12.2 ± 7.8	6.0 ± 4.2	0. 02	7.5 ± 0.7	0.4	5.9 ± 4.4	0. 02

Note: Length of admissions are reported as mean ± SD in days; p‐values are for the preceding columns compared against cumulative length of admission for staged bilateral nephrectomies. Bold values are statistically significant.

3.4. Renal Cell Carcinoma

Of the 77 kidneys removed from 52 ADPKD patients, a histopathological diagnosis of renal neoplasia, both benign and malignant, was made in 10 kidneys from nine individual patients. RCC was histopathologically diagnosed in eight surgically removed kidneys from six ADPKD patients. The patient characteristics and features of RCC lesion(s) including size, Fuhrman grade, side(s) of kidney(s) involved, indication of nephrectomy, and extent of disease involvement (TNM staging) at the time of diagnosis are summarised in Table 6. Of note, four of six patients had multifocal RCC lesions and two had bilateral RCC involvement. Two patients had distant metastasis. One patient (Case 4) was found to have both benign papillary adenoma and clear cell RCC in his surgically removed kidney.

TABLE 6.

Clinical, histopathological and staging details of ADPKD patients with renal cell carcinoma.

No	Age/sex	Indication of nephrectomy	RCC subtype	Number of lesion	Side	Size (mm) a	Fuhrman grade	TNM staging	Seen on prior imaging
1	52/M	For space	Papillary	1	L	8	Low	T2aN0M0	No
2	52/M	Symptom control	Papillary	6	Bilat	25	1–4	T1aN0M0	No
3	59/M	For space	Clear cell	2	Bilat	175	4	T4N1M1	? b
4	64/M	For space	Clear cell	3	R	3	1–2	T1aN0M0	No
5	57/M	Suspicious lesion	Clear cell	3	L	70	4	T3aN0M1	Yes
6	74/F	Suspicious lesion	Clear cell	1	L	10	1	T1aN0M0	Yes

Abbreviations: Bilat: bilateral; F, female; L, left; M, male; R, right; RCC, renal cell carcinoma.

^a Size refers to the largest dimension of the largest carcinoma if multiple lesions were present.

^b Imaging records could not be sourced for Case 3.

Only two patients (Cases 5 and 6) had preceding imaging suggestive of renal malignancy. The remaining patients were incidentally diagnosed with RCC following histopathological examination of their surgically removed kidney(s), with most of these nephrectomies being performed to create space for transplantation. One patient (Case 2) had staged bilateral nephrectomy. Histopathological examination following his first nephrectomy found RCC despite a negative pre‐operative contrast‐enhanced CT. A gadolinium‐enhanced MRI undertaken prior to his second nephrectomy was also negative, though subsequent histopathological examination also found RCC.

3.5. Hepatic Involvement

Of interest, 31 of our 52 ADPKD patients had liver involvement, ranging from localised, countable numbers of cysts to extensive, innumerable cysts. They also varied in size: some hepatic cysts were sub‐centimetre in size, whilst others were significantly larger. The largest liver cyst in one of our ADPKD patients measured 20 × 27 × 26 cm (Figure 2c lower panel). This patient had recurrent pain and febrile illness with no other attributable source, requiring deroofing of this liver cyst and drainage of 7.7 L cystic fluid. Laboratory cultures were positive for vancomycin‐resistant Enterococcus (VRE) and Pseudomonas spp. Despite some of our patients having extensive cystic liver disease, none from this cohort had liver failure requiring consideration of simultaneous liver–kidney transplantation.

4. Discussion

Our study revealed valuable insights into patient characteristics, surgical considerations and outcomes of nephrectomy/ies among ADPKD patients who had undergone the procedure at our centre over the last 26 years, as compared to non‐ADPKD patients requiring the same procedure. These findings have implications for the listing of ADPKD patients for nephrectomy/ies and their peri‐operative management.

Overall, polycystic nephrectomies were safe and effective in creating space for transplantation allografts, removing the source of acute and chronic pain caused by enlarged cysts or cystic haemorrhage, relieving mass effect on other organs and removing radiologically diagnosed malignancy. Nephrectomy to remove septic focus may be limited by the adequacy of imaging to confidently determine the exact source of infection/colonisation against numerous kidney cysts and may necessitate a subsequent contralateral nephrectomy in the case of recurrent urosepsis or pyelonephritis. In such situations, the possibility of a colonised bladder, incomplete clearance of infection especially if multiresistant organism(s) were involved, and that of vesicoureteral reflux (including into the transplant graft) [9, 10, 11] also require consideration.

While our ADPKD patients were more likely to have hypertension pre‐nephrectomy, they were also at a significantly higher risk of post‐operative hypotension. 20% of patients were admitted to intensive care following polycystic nephrectomy/ies; more than half of these patients required inotropic support. In a separate cohort of patients who underwent simultaneous polycystic nephrectomy/ies and kidney transplantation at our centre, most post‐operative admissions to intensive care were also due to post‐operative hypotension [12]. Intra‐operative blood loss (both intrinsic blood stored in the kidney(s) and blood loss during surgical dissection) and post‐operative blood loss (especially in patients with renal failure and dysfunctional platelets) are one aetiology for post‐operative hypotension following polycystic nephrectomies, with our ADPKD patients at higher risk of post‐operative anaemia and more likely to require packed red blood cell transfusions. Nevertheless, the propensity for post‐operative hypotension in polycystic nephrectomy is also multifactorial, with likely contribution from removal of extrinsic IVC compression [13] and sustained activation of the intrarenal renin‐angiotensin‐aldosterone system. While surgeons aim to preserve the adrenal glands during nephrectomy/ies, there is also a component of adrenal stunning due to handling, as illustrated by one of our ADPKD patients described above.

While occurring to the same extent as non‐ADPKD patients, it is worth noting that 18% of our ADPKD patients had post‐operative hyperkalaemia and 10% required unplanned dialysis; arteriovenous fistula thrombosis occurred in 5% of our ADPKD patients post‐operatively. While post‐operative AVF thrombosis was considered a provoked event in our separate report of thromboembolic events in this study cohort, we found ADPKD to be a risk factor for unprovoked AVF thrombosis [3, 8]. Along with the increased risk of intracranial aneurysms in ADPKD patients [4] and their dialysis/AVF dependency, these findings have implications for the peri‐operative management of anti‐hypertensives, anaesthetic management intra‐operatively [14], and the optimal blood pressure range to be maintained peri‐operatively in order to balance the risks of hypertension‐provoked perioperative aneurysmal rupture and the risks of losing dialysis access due to hypotension‐provoked AVF thrombosis [3]. Continuing aspirin over the peri‐operative period may be beneficial for ADPKD patients in preventing AVF thrombosis and, along with statins, in stabilising thus preventing aneurysmal rupture.

Gastrointestinal manifestations including GORD and hernia commonly resolved or improved following nephrectomy in our ADPKD patients, likely due to alleviation of intra‐abdominal pressure following removal of enlarged polycystic kidneys. This is consistent with a previous survey finding improved quality of life in ADPKD post‐nephrectomy, with patients who received bilateral nephrectomy benefiting more compared to unilateral nephrectomy [15]. Surveyed retrospectively, one in five of these ADPKD patients would prefer to have had bilateral nephrectomies [15], which may be driven by its aesthetic effect as well as the potential benefits on their daily function, lifestyle, and wellbeing, as it is common that ADPKD patients are unable to undertake certain activities like bending down, gardening, etc.

Our ADPKD patients were more likely to require bilateral nephrectomies and/or open nephrectomies. Examining ADPKD patients requiring bilateral nephrectomies, a recent systematic review found staged nephrectomies to have an increased cumulative operative time and risk of blood transfusions, with simultaneous bilateral nephrectomies showing no apparent adverse transplantation outcomes [16]. Our study was consistent with this in that ADPKD patients who underwent staged bilateral nephrectomies had a higher cumulative length of admission, though our study was underpowered to detect any significant differences in other outcome measures. On the other hand, simultaneous bilateral nephrectomies undertaken with other concurrent surgical procedures may complicate the post‐operative course and lead to morbidity, as illustrated by one of our patients who underwent bilateral nephrectomies, failed allograft nephrectomy and abdominoplasty. This is consistent with a prior study which found simultaneous bilateral nephrectomy and kidney transplantation to result in higher acuity care and longer admission post‐operatively, compared to patients who underwent kidney transplantation only [17].

Surgeons at our centre prefer simultaneous bilateral nephrectomies through an open trans‐peritoneal approach, via a midline or transverse abdominal incision, especially when pre‐operative imaging reveals very enlarged polycystic kidneys occupying most of the intra‐abdominal space and extending down to the pelvic brim, which usually pose a challenge for laparoscopic removal and increase procedure time. This is confirmed in a systematic review and meta‐analysis, in which laparoscopic nephrectomies were found to be undertaken for smaller kidneys, require longer operative time but potentially have fewer complications and require a shorter hospital admission compared to open nephrectomies [18]. More recently, hand‐assisted laparoscopic nephrectomy has been described as a technique to reduce the invasiveness of surgery for massive polycystic kidneys that are unsuitable for laparoscopic nephrectomy [19]. Regardless of the surgical approach, simultaneous bilateral nephrectomies avoid the need for a subsequent operative procedure when there may be adhesions in the peritoneal cavity after the initial surgery, whereas nephrologists at our centre prefer unilateral nephrectomy especially if patients continue to have native urine output, as this may reduce the need for dialysis, fluid restriction, and the requirement for erythropoietin/red blood cell transfusion, though functional studies to verify individual kidney function may be required to inform such an approach. This difference in preference is usually resolved at a multi‐disciplinary meeting considering the risks and benefits for each patient.

One possible approach is to offer bilateral nephrectomies to suitable patients, with the option to abandon contralateral nephrectomy if the patient becomes unstable intra‐operatively; whereas patients who may not be fit enough to undergo simultaneous bilateral nephrectomies and/or other concurrent procedures could be initially prioritised for unilateral nephrectomies, which reduces the need and length of dialysis and also presents a surgical stress test that informs the suitability and planning process for any subsequent major procedures, including transplantation. An enhanced recovery after surgery (ERAS) protocol is also implemented for all our patients post‐operatively [20].

It is unclear why more ADPKD patients received donation after circulatory death, though it was also observed in another large study [5]. In contrast to another single‐centre study [21], our proportion of living donors for ADPKD patients was not significantly higher, despite the lead time afforded. As living unrelated donors at our single‐centre experience tend to be the spouses of patients requiring transplantation, we postulate that considerations regarding the potential need for future kidney donation to their children may have contributed.

We have separately reported two other extrarenal manifestations of clinical significance: thromboembolic events and intracranial aneurysms [3, 4]. Hereon, we discuss another significant finding worthy of attention among ADPKD patients, particularly those who are candidates for transplantation (thus requiring immunosuppression): RCC.

RCC was histopathologically diagnosed in 11.5% (just over one in every 10) of our ADPKD patients who underwent nephrectomy/ies and 10.3% (one in every 10) of our surgically removed polycystic kidneys, which appears to be higher than a previous report from a histopathological registry [22], but comparable to another study in which 11 solid tumours were found in 89 resected kidneys [23]. All 11 lesions in the latter study were small and of pT1a staging and Fuhrman nuclear grade 1–2 [23], whereas half of our patients had RCC lesions exceeding the previously reported mean tumour size and of higher Fuhrman nuclear grade. Three of our patients were also incidentally diagnosed with RCC(s) following negative pre‐operative imaging. Our case series therefore adds to current available evidence by demonstrating (i) a larger proportion of higher Fuhrman grade RCC lesions, and that (ii) malignant lesions in most patients were not seen on prior radiological studies, highlighting that imaging, including contrast‐enhanced CT and MRI, is not conclusive in ruling out renal malignancies in ADPKD.

The difficulty in reaching a clinical suspicion of RCC is likely in part due to its asymptomatic, clinically occult nature, but also because symptoms typical of RCC (haematuria, flank pain and palpable mass(es)) are common in ADPKD patients [24]. Exclusion of RCC in ADPKD via non‐invasive screening (including ultrasonography, contrast‐enhanced CT and MRI) is difficult given the altered appearance of polycystic kidneys, which may be complicated by cystic haemorrhage, calcification, or internal debris. Renal arteriogram had previously been documented as a way to further investigate suspicious masses [25, 26], but the relatively invasive nature and requirement for contrast for such studies will likely make it less preferable in ADPKD patients with renal impairment, a degree of residual renal function, but not already on renal replacement therapy. More recently, diffusion weighted sequence on MRI has been reported as a non‐invasive investigation to differentiate RCC from polycystic renal parenchyma [27], though further clinical application, experience, and validation are required. Our finding of incidental RCC diagnoses on pre‐transplantation nephrectomies (including cases with lymphovascular invasion and/or distant metastases) along with the added risk of multifocality and bilaterality of RCC in ADPKD, as seen in our series and prior studies [28, 29, 30], reinforces the concerns raised by authors advocating for bilateral native nephrectomy to definitively exclude RCC undiagnosed on imaging prior to asynchronous renal transplantation [31], given the need for immunosuppression following transplantation and that the course of untreated RCC may be difficult to predict with immunosuppression.

The finding of co‐existent benign adenoma and RCC in one of our patients is consistent with previous reports [22]. Based on a higher proportion of kidneys simultaneously harbouring both papillary adenomas and papillary RCCs, papillary adenomas had been postulated as a precursor to papillary RCCs [32]. On the other hand, there have also been reports of kidneys simultaneously harbouring both papillary RCCs and clear cell RCCs [23, 29, 30, 33]. As more is known of their respective pathogenesis, there is increasing speculation that ADPKD predisposes patients to RCCs, with shared molecular pathways in disease development and the accumulation of mutational hits presenting an emerging hypothesis for RCC carcinogenesis [34, 35].

The strength of our study includes the longitudinal, multidimensional assessment of patient outcomes following nephrectomy over a 26‐year period, identifying important findings, clinical caveats, and considerations relevant to the peri‐operative practices of surgeons who offer polycystic nephrectomies as part of their practice. Incorporating these, a patient‐centred framework for consideration when evaluating and counselling ADPKD patients for elective nephrectomy/ies and their peri‐operative management is proposed in Figure 3. One limitation of this study is that its retrospective nature may have inherently introduced a selection bias for patients who were medically fit to proceed with nephrectomy/ies despite their age and comorbidities, as well as patients' willingness to accept medical recommendations for nephrectomy/ies, which represents a significant life‐changing event given the subsequent dialysis dependence and need for fluid restriction. As such, the generalisability of our findings when assessing ADPKD patients referred for elective nephrectomy/ies (especially older, frail patients) may be limited.

FIGURE 3.

Considerations for patients and surgeons when deciding whether to proceed with polycystic nephrectomy/ies and factors influencing peri‐operative management.

5. Conclusion

Examining ADPKD patients and non‐ADPKD patients who underwent nephrectomy/ies at our centre over the last 26 years, we found polycystic nephrectomies to be safe and effective. However, it was noted that ADPKD patients were at higher risk of post‐operative hypotension, anaemia, requiring blood transfusions, and intensive care admission. ADPKD patients were also older and more likely to have ESRF requiring renal replacement therapy, hypertension, and gastrointestinal symptoms at the time of first nephrectomy. They were more likely to require bilateral and/or open nephrectomies, and when transplanted, more likely to receive allografts donated after circulatory death. Staged bilateral nephrectomies resulted in increased cumulative admission time for both ADPKD and non‐ADPKD patients.

RCC may be of higher prevalence in our ADPKD patients, and our cohort consisted of a larger proportion of higher Fuhrman grade RCC lesions, with most malignant lesions not detected on prior radiological studies. Our study reiterates the added risk of multifocality and bilaterality of RCC in ADPKD, making this an important factor for consideration among ADPKD patients being evaluated for nephrectomy/ies, especially those who are candidates for transplantation.

Author Contributions

Joel Ern Zher Chan: conceptualization, data curation, formal analysis, investigation, methodology, validation, visualization, writing – original draft, writing – review and editing. Kate S. Olakkengil: data curation, formal analysis, writing – review and editing. Shantanu Bhattacharjya: conceptualization, formal analysis, investigation, supervision, validation, writing – review and editing. Santosh Antony Olakkengil: conceptualization, formal analysis, investigation, methodology, supervision, validation, writing – review and editing.

Disclosure

The authors have nothing to report.

Ethics Statement

The study was considered and approved by the Central Adelaide Local Health Network Human Research Ethics Committee, reference number 18505.

Conflicts of Interest

The authors declare no conflicts of interest.

Chan J. E. Z., Olakkengil K. S., Bhattacharjya S., and Olakkengil S. A., “Autosomal Dominant Polycystic Kidney Disease Patients Requiring Nephrectomy: Characteristics and Surgical Considerations,” ANZ Journal of Surgery 95, no. 7‐8 (2025): 1605–1616, 10.1111/ans.70192.