Table 2.
Studies reporting proteinuria related to venous congestion or elevation of intra‐abdominal pressure
| Study | Design | Cohort | Methods | Findings |
|---|---|---|---|---|
| Bradley et al., 1947 63 | Prospective interventional single centre | 17 healthy individuals; mean GFR 115 ± 19 mL/min | External abdominal compression at 80 mmHg (resulting in intra‐abdominal pressure approx. 20 mmHg), invasively measured renal venous pressure in 9 individuals | Transient proteinuria and renal venous pressure elevation (from mean 5.8 to 18.3 mmHg) during abdominal compression |
| Vesely et al., 2001 95 | Prospective interventional single centre | 24 patients with HF with reduced ejection fraction and New York Heart Association functional class III; patients with serum creatinine levels >1.5 mg/dL were excluded | Infusion of long‐acting natriuretic peptide, vessel dilator, and kaliuretic peptide for a duration of 60 min | 2‐fold to 7‐fold increase in albuminuria, 2‐fold to 5‐fold increase in proteinuria, and 25‐fold to 40‐fold increase in urinary β2‐microglobulin (marker of proximal tubular reabsorption); authors postulate that part of the mechanism of the observed enhanced protein excretion is the inhibition of proximal tubular reabsorption of protein |
| Koyama et al., 2013 97 | Prospective observational single centre | 115 patients admitted for acute HF (preserved and reduced left ventricular ejection fraction); mean baseline estimated GFR 48 ± 23 mL/min/1.73 m2 | Spot urinary albumin‐to‐creatinine ratio measured on Days 1 and 7 of hospitalization | Increased albuminuria at admission with significant decrease within 7 days of treatment of cardiac decompensation; these changes were paralleled by decreases in N‐terminal pro‐b‐type natriuretic peptide levels, but not with baseline nor with changes in renal function |
| Navaneethan et al., 2016 98 | Prospective observational multi‐centre | 2959 patients with non‐dialysis‐dependent chronic kidney disease (estimated GFR: 20–70 mL/min/1.73 m2) and preserved left ventricular ejection fraction; PH present in 21%; patients with New York Heart Association functional class III/IV HF were excluded | Median 4.1 year follow‐up evaluating cardiovascular and renal outcomes, and all‐cause mortality | 24 h proteinuria comparable between those with and without PH (mean, 200 vs. 200 mg; P = 0.10), the overall higher‐than‐normal values likely reflecting the high prevalence of concomitant cardiovascular disease and diabetes in both cohorts |
| Jotwani et al., 2018 100 | Prospective observational dual centre | Random sample of 776 participants including cardiovascular disease and HF cases | Median 12.4 year follow‐up evaluating incident cardiovascular disease, HF, and all‐cause mortality | Higher urinary alpha‐1 microglobulin and urinary neutrophil gelatinase‐associated lipocalin levels are associated with elevated risk of incident cardiovascular disease and all‐cause mortality; no significant association with HF |
| Husain‐Syed et al., 2019 74 | Prospective observational single centre | 205 patients with suspected or prediagnosed PH undergoing right heart catheterization; PH excluded in 40 patients; 165 patients diagnosed with PH group 1–5 | Evaluation of baseline morning spot urinary protein‐to‐creatinine, albumin‐to‐creatinine, and α1‐microglobulin‐to‐creatinine ratios; median 1 year follow‐up evaluating composite endpoint of PH progression | Gradual increase in proteinuria, albuminuria, and α1‐microglobulin excretion with increasing severity of congestion, although the increase remains within the physiological range |
| Nickel et al., 2019 93 | Prospective observational dual‐centre | 283 patients with pulmonary arterial hypertension, 18 unaffected carriers of mutations in the gene encoding bone morphogenetic protein receptor type 2, 68 healthy controls (2 independent cohorts); patients with diabetes mellitus and estimated GFR < 60 mL/min/1.73 m2 were excluded | Morning spot urinary albumin‐to‐creatinine ratio | Gradual increase in albuminuria with increasing severity of congestion, although the increase remains within the physiological range (below the threshold of microalbuminuria) and is statistically non‐significant in this study; urinary albumin‐to‐creatinine ratio > 10 μg/mg significantly associated with higher odds of death or lung transplantation |
| Garimella et al., 2019 99 | Prospective multi‐centre open‐label clinical trial | Patients with high systolic blood pressure and high risk for cardiovascular events; 2337 selected non‐diabetic patients with estimated GFRs < 60 mL/min/1.73 m2; patients with HF were excluded | Median 3.8 year follow‐up evaluating a composite cardiovascular outcome | Lower urinary uromodulin excretion (which is associated with higher odds of tubular atrophy and fibrosis 151 ) and higher urinary alpha‐1 microglobulin levels are associated with elevated risk of HF |
| Experimental | ||||
| Winton 1931 76 | Prospective interventional | One dog model with isolated perfused kidneys | Ligature of renal veins (renal venous pressure of >20 mmHg) | Gradual increase in proteinuria during renal venous pressure elevation; proteinuria normalizes when renal venous pressure returns to baseline |
| Doty et al., 1999 83 | Prospective interventional | Eight swine | Renal vein constriction (renal venous pressure of baseline and 30 mmHg) | Renal venous pressure elevation leads to significantly increased proteinuria, with the finding being reversible when venous pressure returns towards baseline |
| Shimada et al., 2018 78 | Prospective interventional | Intubated and anaesthetized Sprague–Dawley rats vs. sham‐operated rats | Ligature by suture of inferior vena cava between renal veins to allow comparison of congestive left kidneys with non‐congestive right kidneys | 3 days after surgery, significantly increased urinary albumin‐to‐creatinine ratio in the congestive left kidneys, potentially associated with observed podocyte injury and slit diaphragm disruption |
| Cops et al., 2018 101 | Prospective interventional | Intubated and anaesthetized Sprague–Dawley rats (n = 7) vs. sham‐operated rats (n = 6) | Permanent surgical constriction (20 gauge) of thoracic inferior vena cava (increasing central venous pressure to a mean of 17 mmHg) | 12 weeks after surgery, plasma creatinine, plasma cystatin C, urinary albumin, glomerular surface area, and width of Bowman capsule increased significantly in the inferior vena cava group compared with the sham group; no difference in the acute tubular damage biomarker kidney injury molecule‐1 |
GFR, glomerular filtration rate; HF, heart failure; PH, pulmonary hypertension.