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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1388-1396
Nephrotic syndrome in elderly: Etiologies, management, and prognosis

Department of Nephrology, Dialysis and Transplantation, Charles Nicolle Hospital; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

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Date of Web Publication4-May-2022


The elderly population has significantly increased in the world. Nephrotic syndrome (NS) is one manifestation of glomerular nephropathy in the elderly. The objective of our study is to determine NS particularities in the elderly and to identify the factors predicting progression to chronic end-stage renal disease (ESRD). This is a retrospective and descriptive study, carried out between January 1, 1975 and December 31, 2017. It includes participants aged 65 years old or over hospitalized for NS. A multivariate study was carried out and the dependent variable was the evolution to ESRD. We studied 115 patients with an average age of 71 ±5 years (65–83) and a sex ratio (male/female) of 1.7. Twenty-three percent of patients were diabetic. The median proteinuria was 4.7 g/L (3–19.5). NS was impure in 89.5% of patients. Renal biopsy was performed in 45 patients (39.13%). NS was secondary in 65.2% of cases mainly to amyloidosis (35.6%). Idiopathic nephropathy was dominated by membranous nephropathy (9.5%). Treatment was etiopathogenic in only 18 patients (15.6%). At the end of follow-up, 15.8% of patients achieved complete or partial remission and 56.6% progressed to ESRD. The multivariate study found as independent risk factors of progression to ESRD: uremia >17 mmol/L [adjusted odds ratio (aOR) = 33.2 (1.3–837.7); P <0.05],, phosphoremia ≥1.6 mmol/L [aOR = 22.1 (1.8–266.5); P <0.05], serum potassium ≥4.3 mmol/L (aOR = 24.7 (2.4, 251.5); P <0.01], extra-renal signs [aOR = 38.9 (2.4–634.3); P = 0.01], secondary nephropathy [aOR = 74 (3.1–1788.2); P <0.01] and membranoproliferative glomerulonephritis [aOR = 48 (1.4–1675.5); P <0.05]. The protective factors were hemoglobinemia ≥9.3 g/dL [aOR = 0.007 (0–0.2); P <0.01], kidneys well differentiated [0.032 (0.003–0.4); P<0.01] and treatment with two diuretics [aOR = 0.03 (0.00–30.4); P <0.01]. It is important to recognize the spectrum of kidney diseases in the elderly to improve the progression factors to ESRD.

How to cite this article:
Gorsane I, Ayed TB, Hajji M, Barbouch S, Abdallah TB. Nephrotic syndrome in elderly: Etiologies, management, and prognosis. Saudi J Kidney Dis Transpl 2021;32:1388-96

How to cite this URL:
Gorsane I, Ayed TB, Hajji M, Barbouch S, Abdallah TB. Nephrotic syndrome in elderly: Etiologies, management, and prognosis. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1388-96. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1388/344759

   Introduction Top

Epidemiologic studies show that 11% of the world’s population is over 60 years of age. This is projected to increase, by 2050, to 22% of the population.[1]

Elderly people are affected by the same kidney disease that young patients, but their clinical course and morphological manifestations can be affected by aging which is associated with a decrease in glomerular filtration rate of approximately 0.8–1.7 mL/min/year.[2]

Glomerulopathies represent up to 25% of cases of renal failure in the elderly.[3] Nephrotic syndrome (NS) is an clinical entity characterized by massive proteinuria, hypoalbuminemia, and edema. It is not rare in the population of over 65 years of age.

Incidence of NS in the elderly has been widely recognized with the popularization of renal biopsy and the elongation of human life. The prognosis of senile NS seems to be worsened by aggressive therapeutics. Relatively little is known about NS in older adults and factors of disease progression to end-stage renal disease (ESRD) have been little studied.

The aim of this study was to report the causes of NS and their clinical presentations in elderly patients and to identify the factors of progression to ESRD.

   Methods Top

This is a retrospective, descriptive and analytical study carried out in the department of Nephrology in Charles Nicolle Hospital in Tunis between January 1, 1975 and December 31, 2017; either a period of 47 years. The study included patients aged 65 and over, having a NS and hospitalized in our department.

The NS was defined as proteinuria >3 g/24 h, plasma protein <60 g/L and albuminemia <30 g/L.[4]

Creatinine clearance was calculated according to the modification of diet in renal disease study (MDRD) formula.[5]

Complete remission (CR) was defined by a rate of proteinuria <0.3 g/24 h and albuminemia ≥30 g/L.[6]

Partial remission (PR) was defined by albuminemia ≥30 g/L and persistent proteinuria ≥0.3 g/24 h.[6]

Relapse was defined by the recurrence of proteinuria ≥3 g/24 h in a patient in CR or PR.[6]

The clinical records of patients were retrieved. Renal tissues obtained at biopsy were examined by light microscopy and immuno-fluorescence study (using anti-IgG, IgA, IgM, C1q, C3, and fibrinogen antibodies). The histological classification used in this report was based on WHO classification (Churg and Sobin 1982).

Data entry and analysis were carried out with IBM SPSS Statistics version 22.0 software (IBM Corp., Armonk, NY, USA). Qualitative variables were expressed in number and in percentage. Quantitative variables were expressed in average and median with the minimum and maximum value. An analytical study was performed to investigate the predictors of progression to ESRD.

For quantitative values, we used the “receiver operating characteristics” (ROC) curve. We determined the “cutoff, value, which presents the best sensitivity and specificity for each variable studied, using the Youden index. The quantitative variables were thus transformed into qualitative variables, which are easier to interpret.

We calculated the optimal thresholds for the variables that were significantly associated with progression to the ESRD.

For univariate analytical study, we used Fisher’s exact test or Chi-square test for theoretical numbers greater than 5. We used as predictors, the variables for which P was less than 0.05.

For each variable studied, we also expressed the gross odds ratio (OR) and the confidence interval (CI).

Multivariate analysis was performed by Wald regression in stepwise fashion descending. The dependent variable was entry into ESRD.

The explanatory variables were the prognostic factors found in the literature, and those retained from our univariate analysis with a degree of significance P <0.25.

The suitability of the model was checked by the Hosmer-Lemeshow test. The predictive power of the model was evaluated by the Nagelkerke R-two and by the “C statistic” or concordance index.

The significance level for defining an independent predictor was set at P-value <0.05. We also expressed for each factor, the adjusted odds ratio (aOR) and CI.

   Results Top

Among the 2659 patients aged 65 years and over and hospitalized in our department during the study period, 192 were hospitalized for NS. The prevalence of NS in the elderly was 7.22%. The average incidence was 6.34 patients per year. Because of unusable files, 77 records were eliminated; 115 patients were selected for the study. The sex ratio (Male/ Female) was 1.7. The mean age at diagnosis was 71 ± 5 years (65-83) with a peak frequency between 65 and 70 years. The patients’ pathological history is presented in [Table 1].
Table 1: Distribution of the population according to pathological history.

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The most frequent discovery circumstances for NS were peripheral edema and renal failure, found in 61% and 40% of cases, respectively. Fifty-four percent of patients had hypertension and 30.4% had hematuria ≥2× on the test strip.

The median proteinuria rate was 4.7 g/24h (3–19.5). The mean protidemia rate was 50.6 g/L ± 6.9 (36–59). The mean albuminemia was 20 g/L ± 6 (6–29).

82.7% of patients had kidney failure. The median creatinine level was 265 μmol/L (48–2188). The median creatinine clearance was 17 mL/min/1.73 m2 (2–127). It was stage 3 kidney failure in 20% of the cases and stage 4 in 62.7% of the cases.

Hypercholesterolemia was found in 66 patients (57.4%) and hypertriglyceridemia in 62 patients (54%).

NS was impure in 103 patients (89.5%). Forty-five patients (39%) had a renal sample for histological examination by biopsy. Among the biopsied patients, the most frequent pathological entities were membranous glomerulonephritis (MGN) (29%), glomerular amyloidosis (24.5%), membranoproliferative GN (MPGN) (17.8%), and minimal change GN (MCGN) (8.9%).

A sternal puncture was performed in 15 patients (13 %) showing the diagnosis of multiple myeloma (MM) in five cases.

Etiological forms of NS including biopsied and nonbiopsied patients are presented in [Table 2].
Table 2: Distribution of the population according to etiologies.

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Amyloidosis represents the first etiology of NS, found in 35.6% of cases. It was AA amyloidosis in 63.4% of the cases; non-AA in 17.1% of cases and untyped in 19.5% of cases.

Treatment was conservative in 84.1% with the use of diuretics, antiplatelet agents and anticoagulants in 80.9%, 40%, and 9.5% of cases, respectively. Renin–angiotensin–aldosterone system (RAAS) blockers were prescribed in 48% of the cases and statins in 6.9% of the cases.

Etiopathogenic treatment was used in 18 patients (15.6%) with corticosteroids alone in 14 patients and in combination with immuno-suppressants (cyclophosphamide) in four patients. Four patients received the melphalan and prednisone for the treatment of MM. Sixty-two patients (54%) needed dialysis.

During evolution, thromboembolic complications were noted in five patients (4.3%) and infectious complications in 55 patients (47.8%). Fourteen patients (12.2%) died by infectious complications.

Nine patients were lost to follow-up after hospitalization. Seven patients died during hospitalization; three of them were at the ESRD. Thus, the evolution was only studied for 51 patients with a median follow-up of 27 months (4–182).

At the end of follow-up, CR of NS was noted in five patients (9.8%), PR in 13 patients (25.5%) and relapses in three cases (2.6%). In patients having had etiopathogenic treatment, 23% of the patients had a CR, 38.5% a PR and 38.5% a persistence of the NS. ESRD was found in 65 patients (56.5%).

The optimal thresholds of the variables that were significantly associated with progression to ESRD are presented in [Table 3].
Table 3: Variables associated with progression to end-stage renal disease.

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The results of the univariate study for risk factors or protectors of progression to ESRD, using the variables created with the thresholds found, are presented in [Table 4].
Table 4: Relationship between the variables created with the thresholds found and the evolution to endstage renal disease.

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Risk factors in multivariate study, with as dependent variable the evolution to ESRD, are shown by the [Table 5].
Table 5: Results of the multivariate study with the evolution toward end-stage renal disease as dependent variable.

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   Discussion Top

The results of our study concluded that the prevalence of NS in the elderly was 7.2% with a median incidence of six patients per year. We identified as risk factors of progression to ESRD: uremia ≥ 17 mmol/L; phosphoremia ≥1.6 mmol/L; serum potassium 𕫥4.3 mmol/L; extra-renal signs; secondary nephropathy and MPGN. The protective factors for progression to ESRD were: hemoglobinemia, kidneys well differentiated on ultrasound and treatment with two diuretics or more.

In the elderly, the definition used for NS is usually that of a young adult. Some authors defined NS in people over 65 by proteinuria ≥3.5 g/24 h and/or proteinuria/urine creatinine ratio ≥3.5 g/g associated with hypoalbuminemia <30 g/L and/or hypoprotidemia <60 g/L.[7]

NS is a common clinical presentation of glomerular nephropathy in the elderly. Its prevalence ranges from 30% to 62.5% in elderly patients with glomerular nephropathies who have had a renal biopsy.[8],[9]

Clinical presentations of older patients with NS were similar to younger patients apart from the age-related decline of renal function, the frequency of comorbidities the higher prevalence of hypertension and the higher risk of developing diabetes mellitus, acute kidney injury and tumors under corticosteroid therapy and/or immunosuppressants. Older age is also a significant risk factor for mortality.[10]

The frequency of renal insufficiency, clearly higher in our series (82.6%)' compared to the most studies in patients over 65 years (61%–75.5%)‘[11],[12] reflects diagnostic delay which would be explained in part by the absence of systematic search for proteinuria in the elderly and the delay in consultation. However, we calculated glomerular filtration rate by the MDRD formula which would not be valid in the elderly.[13]

Renal histology is not only benefit in diagnosis but also of potential value in terms of prognosis and treatment. In our series, 39% of NS had a renal biopsy. It is lower than what is reported in the literature (64.6%).[14]

Primary nephropathies were more frequent, found in 62% to 85% of cases.[8],[9],[10],[11],[12],[13],[14],[15] MGN represents the most frequent histological form.[16] We have found a predominance of secondary nephropathy (65.2% vs. 20% for primary nephropathies). However, in the different studies reported, only patients who have had renal kidney biopsies are studied.[17]

Amyloidosis is the cause of NS in the elderly in 10%–15% of with a predominance of the AL type.[17] The high frequency of amyloidosis found in our series (35.6 %) especially of the AA type, can be partly explained by the endemicity of tuberculosis in our country. Whatever the age, the treatment of NS depends on histological and etiological diagnosis.

Symptomatic treatment with diuretics, RAAS blockers, statins, anticoagulants and anti-aggregates should be initiated in the acute phase of management and maintained until recovery from NS is achieved to prevent complications related to NS, to avoid thromboembolic events and to improve the quality of life of patients.[18]

The etiopathogenic treatment schemes used for biopsy-proven kidney diseases were determined according to pathological changes, urinary protein and renal function based on Kidney Disease Improving Global Outcomes, the treatment scheme for each pathological type was determined and individualized. With regard to immunosuppressive therapy, glucocorticoid was the basic drug. Cyclophosphamide and mycophemolate mofetil were also used in some cases.[19] Rituximab might be a new agent in the treatment of refractory NS, it also could be used as an alternative to conventional immunosuppressive drugs dependent or drugs resistant or as cortisonic savings in the elderly.[20] The prescription of immunosup-pressive therapy in this age group responds to a risk-benefit balance and requires close monitoring.[11],[16]

Therefore, only immunosuppressive therapy was significantly associated with better renal response. Etiopathogenic treatment in our series was used only in 18 patients (15.6%) with corticosteroids alone in 14 patients and in combination with immunosuppressants (cyclophosphamide) in four patients. Advanced age was not a significant predictor of insufficient response or nonresponse.[14],[20] Older patients tend to have fewer relapses and require fewer second agents for the treatment of relapses.[10]

The changes or remission of proteinuria, hypoalbuminemia, hyperlipidemia, and serum creatinine are often used to evaluate the efficacy of clinical treatment.[21]

When untreated or when it resists treatment, the glomerular damage associated with NS can be accompanied by a progressive decrease in renal function, which can progress to the ESRD.[15],[22]

Few studies have carried out a multivariate study in search of independent prognostic factors for progression to ESRD in a elderly with SN. [Table 6] compares the results of our study with data from the literature.[23],[24],[25],[26],[27] Further research in a larger patient population is required to verify these findings.
Table 6: Review of predictive factors for progression to end-stage renal disease in the literature.

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   Conclusion Top

Our management of elderly patients with NS is characterized by a delay in consultation and diagnosis, a diversity of care for patients with limited use of immunosuppressive treatments and a worse prognosis with a large number of people lost to follow-up. Hence, the importance of early care to improve the evolutionary prognosis of this population. Moreover, advanced age alone should no longer make physicians reluctant to perform renal biopsy. It is difficult to compare our results with those found in the literature because of the small size of our subgroups. A study of a larger sample size will be required with a detailed comparison between elderly and young patients.

Conflict of interest: None declared.

   References Top

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Correspondence Address:
Imen Gorsane
Department of Nephrology, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.344759

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