Evaluation of albumin-based proteinuria selectivity index as a substitute for transferrin-based proteinuria selectivity index.

Proteinuria selectivity index based upon α2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases: Technical Note

Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases

Objectives The selectivity index has been proposed in predicting the response to immunosuppressive therapy in nephrotic syndrome and other primary kidney disorders. The aim of this study was to elucidate the predictive value of the selectivity index for the treatment response and renal outcome in patients with lupus nephritis. Methods Forty-four patients with lupus nephritis with selectivity index available at the time of renal biopsy were divided into two groups according to the cut-off value of the selectivity index determined by a receiver operating characteristics curve to differentiate treatment responders from non-responders. The baseline characteristics, overall response rate and renal functional outcome were studied retrospectively, and compared between the two groups. Prognostic factors for achieving remission were identified. Results The cut-off value of the selectivity index was 0.167. The low selectivity index (<0.167) and the high selectivity index (≥0.167) group included 24 and 20 patients, respectively. The overall response rate was significantly higher (88% vs. 50%, P = 0.007) and the rate of progression to end-stage renal disease was lower in the low selectivity index group (0% vs. 15%, P = 0.049). More patients in the high selectivity index group had chronic lesions on renal biopsy ( P = 0.002). The selectivity index was the prognostic factor for achieving overall response based on a multivariate analysis ( P = 0.020). Conclusions A selectivity index ≥0.167 was a strong predictor for a poor treatment response and the presence of chronic lesions on renal biopsy. Further exploration with a larger cohort and longer follow-up period is warranted.

In order to predict the steroid response in lipoid nephrosis (LN), we studied age, sex, proteinuria level, histological features and proteinuria selectivity index (SI; ratio between IgG and transferrin clearances) in 52 LN cases (minimal-change disease: n = 39; focal glomerulosclerosis+IgM nephropathy: n = 13). The multivariate analysis showed that age, sex and proteinuria level were not contributive, whereas histology and SI were. The predictive value of SI was much higher than that of histological type (McFadden's r2: 47% vs. 22%, p < 0.001). Thus, SI should be systemically assessed in idiopathic nephrotic syndrome for reviewing the pathologic classification obtained by histology. However, if its prognostic value is lower than that of selectivity, initial renal biopsy remains necessary for diagnosis in adults.

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy.

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The proteinuria selectivity index (PSI) can predict the response to prednisone in the primary nephrotic syndrome (PNS). To determine the association of prednisone response with the PSI in patients with PNS. With analytical cross-sectional design, pediatric patients with PNS were studied with at least six months of prior follow-up, at the Nuevo Hospital Civil de Guadalajara from 2014 to 2015. They were divided into poor response to prednisone (frequent relapses or resistance) and good response (habitual relapses). PSI was calculated with serum and urinary measurement of IgG and transferrin. Chi square and OR were used, with 95% CI. 67 patients with relapsing PNS were studied. The response to prednisone had been good in 33 (49.3%) and poor in 34 (50.7%). The PSI was ≤ 0.10 mg/mg in 23/67 (34.3%); 0.11-0.19 mg/mg in 15/67 (22.4%); and ≥ 0.20 mg/mg 29/67 (43.3%). 3/34 patients (8.8%) presented ≤ 0.1 mg/mg with poor response to prednisone and 20/33 presented good response (60.6%) (p < 0.001; OR: 0.6; 95% CI, 0.010-20). PSI between 0.11-0-19 mg/mg occurred in 8/34 patients (23%) with poor response to prednisone and in 7/33 with good response (21%). PSI ≥ 0.20 mg/mg resulted in 23/34 patients (67.6%) with poor response to the steroid and in 6/33 with good response (18.2%) (p < 0.001; OR: 9.4; 95% CI, 3.01-29.42). In children with PNS, a PSI ≥ 0.20 mg/mg was associated with a poor response to prednisone treatment and a PSI ≤ 0.10 mg/mg with a satisfactory response.

A modern approach to selectivity of proteinuria and tubulointerstitial damage in nephrotic syndrome

Proteinuria selectivity index (PSI) is a relatively simple test which in temperate countries has been used to select nephrotic children most likely to respond to corticosteroid therapy. It has been advocated that in nephrotic children aged 1 to 5 years renal biopsy could be avoided by doing PSI. The purpose of this study was to determine whether there is a correlation between PSI and kidney histology in nephrotic children in tropical Africa and whether PSI alone could be used in planning their treatment. PSI and renal biopsy were done on 40 nephrotic children. Histologic classification of kidney biopsies is presented and related to PSI values. No correlation was found between PSI values and histologic diagnoses.

No available prognostic factor was identified for atherosclerotic renovascular stenosis (ARAS) patient who undergo the percutaneous revascularization therapy. This is a case of 68-year-old ARAS patient associated with hypertension and massive proteinuria, who exhibited progressive aggravation of renal dysfunction. His proteinuria selectivity index (SI) was only 0.08. Then the stenosis was treated by percutaneous transluminal angioplasty of the renal artery (PTRA) and stenting. After 2-year follow up, all symptoms including renal dysfunction and uncontrolled hypertension was well-controlled. As no reliable predictors of clinical response have been identified yet, SI might be a simple prognositic index for ARAS patients undergone the revascularzation therapy.

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n = 39) and high-PSI groups (PSI ≥0.243, n = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02–3.85 and HR 1.75; 95% CI 1.01–3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01–0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

Objectives: Nephrotic range proteinuria (NRP) and nephrotic syndrome (NS) are common manifestations of glomerular diseases across age groups. Kidney biopsy remains the gold standard for diagnosis. However, in resource-limited settings, the availability of electron microscopy (EM) is restricted, necessitating evaluation of its diagnostic utility. This study aims to assess the histopathological spectrum of glomerular diseases in pediatric and adult patients presenting with NS and NRP, and to evaluate the diagnostic utility of EM. Methods: A total of 180 consecutive renal biopsies were analyzed according to the 2016 Renal Pathology Society Consensus guidelines. Results: Of the 180 patients, 36 (20%) were pediatric and 144 (80%) were adult. NS was more common in children (72.2%), while nephrotic-range proteinuria (NRP) without full-blown NS predominated among adults (52.8%). In pediatric patients with NS, the most frequent diagnosis was minimal change nephropathy (MCN) (38.5%), followed by focal segmental glomerulosclerosis (FSGS) (19.2%). Among pediatric NRP cases, MCN remained the most common (27.7%), with lupus nephritis (22.3%) and FSGS (16.6%) also notable. In adults with NRP, the leading diagnosis was FSGS (27.1%), followed by IgA nephropathy, membranous nephropathy (MN), and amyloidosis, each accounting for 11.8% of this subgroup. Among adults with NS, FSGS remained predominant (26.5%), followed by amyloidosis (17.6%) and MN (14.7%). EM contributed to diagnosis in 29.4% of all cases ( n = 53), being essential for diagnosis in 12.2% and supportive in 17.2%. EM was particularly crucial in identifying lupus podocytopathy, dense deposit disease, Alport syndrome, and early-stage MN, which may not be definitively diagnosed by light or immunofluorescence microscopy alone. Conclusion: FSGS and MCN are the most common causes of NS across age groups. The findings highlight a shifting spectrum of glomerular diseases, consistent with national and global trends. Although not routinely feasible, EM provides significant diagnostic value in selected cases. Preserving tissue for potential EM evaluation is strongly recommended, especially in ambiguous or complex presentations.

Selectivity index (SI) of proteinuria, calculated using the clearance ratio of immunoglobulin G to transferrin, predicts the response to glucocorticoids in patients with nephrotic syndrome. However, there is disagreement regarding the suitability of SI. Therefore, alternate indices should be considered. This study investigated whether or not selectivity index protein fraction (SIPF) was inferior to SI for the prediction of the response to glucocorticoids. Forty-nine patients with nephrotic syndrome were evaluated. On the basis of molecular weight and protein fraction, as an inexpensive substitute for SI, the clearance ratio of the albumin to γ fractions measured in serum and urine protein fractions was defined as SIPF. The quality of SIPF was examined. Moreover, the best cutoff value of SIPF was determined; and SIPF distribution, according to histopathological diagnosis by renal biopsy, was examined. SIPF was strongly correlated with SI (r = 0.79, P < 0.001). The area under the receiver operating characteristic (ROC) curve of SIPF and SI was not significantly different (P = 0.18). The best cutoff value of SIPF was 0.45. In the group with SIPF > 0.45, only two patients with minimal change disease (MCD) achieved complete remission. In the group with SIPF ≤ 0.45, all patients with MCD achieved complete remission, although eight patients with other histopathological diagnoses did not achieve complete remission. Analysis of protein fractions as a substitute for SI may be useful for predicting response to glucocorticoids in patients with nephrotic syndrome.

Minimal change disease (MCD) accounts for 10-15% of idiopathic nephrotic syndrome in adults.Patients typically present with nephrotic range proteinuria, hypertension, microscopic hematuria and can even progress to acute renal failure.MCD can be primary (idiopathic) or secondary from etiologies such as cancer, medications, autoimmune conditions and infections.The link between infectious etiologies for MCD is important to recognize, since MCD tends to show a good response to treatment of the underlying cause.Influenza A has been reported as a secondary cause of MCD and rarely, influenza A, not B, can also present with liver failure.We present an atypical case of a 60-year-old female with no past medical history who presented with liver failure along with acute kidney injury and nephrotic range proteinuria.