| Abstract|| |
The reported causes of nephrotic syndrome (NS) varies between different countries. In this retrospective study, we aimed to evaluate the underlying causes of NS in adult patients who underwent renal biopsy in a region of Morocco and we also determined the distribution of histopathological diagnoses with regard to the age subgroups and genders from January 2007 to December 2016. Patients were divided into four groups according to age at the time of renal biopsy. A total of the 257 patients with NS were included in this study. The mean age of the patients was 40.9 ± 16.7 years; male gender was preponderant (61.9%). One hundred and sixty-six (64.6 %) and 81 (35.4%) patients were diagnosed as primary and secondary glomerulonephritis, respectively. The most common diagnosis in NS was membranous nephropathy (MN) (22.2%), followed by minimal change disease (MCD) (20.6%), and lupus nephritis (LN) (13.6%). Among the patients aged 15–30, 31–45, 46–60, and >61 years, the most common cause of NS was MCD (32.1%), MN (29.6 %), MN (26.1%), and amyloidosis (AM) (28.2%), respectively. The proportion of patients with MCD and LN decreased in parallel with patient age and the proportion of patients with renal AM increased in parallel with patient age. Among the female patients aged 15–30 and 31–45 years, LN was the leading cause of NS (41.5 and 36.7%, respectively). Among the male patients aged 15–30 years, MCD was the leading cause of NS (43.2%). Our study over 10 years represents an important data of regional variations of glomerular diseases presenting with adult-onset NS.
|How to cite this article:|
Zajjari Y, Aatif T, Kawtar H, Benbria S, Montasser D, El Kabbaj D. Histopathological study of nephrotic syndrome in adults: A Moroccan report. Saudi J Kidney Dis Transpl 2018;29:643-8
|How to cite this URL:|
Zajjari Y, Aatif T, Kawtar H, Benbria S, Montasser D, El Kabbaj D. Histopathological study of nephrotic syndrome in adults: A Moroccan report. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Aug 14];29:643-8. Available from: https://www.sjkdt.org/text.asp?2018/29/3/643/235193
| Introduction|| |
Nephrotic syndrome (NS) is a clinical syndrome showing specific features of heavy pro-teinuria and hypoalbuminemia or hypoproteinemia as its consequence. It is caused by increased permeability of serum protein through the damaged basement membrane in the renal glomerulus. The definition of this syndrome includes both massive proteinuria (>3.5 g/day) and hypoalbuminemia (serum albumin <3.0 g/dL). It is the indication in approximately 40% of patients undergoing renal biopsy worldwide. It usually suggests the presence of glomerular disease and is associated with systemic complications including coagulopathy, thrombosis, and metabolic derangement. However, the reported causes of NS varied between ethnicities, age, and gender. This may reflect possible differences in disease prevalence, genetic background, and renal biopsy indications.
Unfortunately, there are no data on the spectrum of diseases causing NS in Morocco as there is no national renal biopsy registry. Thus, the aim of this study was to evaluate the causes of NS in adult patients in a region of Morocco and determine the spectrum of pathologies according to different age subgroups and genders at the Military Hospital Mohammed V, Rabat, Morocco between January 2007 and December 2016.
| Materials and Methods|| |
This was a retrospective study of adult patients who underwent renal biopsy for investigation of NS in the Military Hospital Mohammed V in Rabat, Morocco, between January 2007 and December 2016.
NS was defined as proteinuria >3.5 g/day by 24 h urine collection or spot urine total protein-to-creatinine-ratio>3.5 mg/mg and serum albumin <30 g/L.
All adult patients aged >15 were included in this study. Exclusion criteria were inadequate biopsies [<5 glomeruli in the specimen for light microscopy (LM) or absence of a glomerulus in immunofluorescence (IF)], repeat biopsies, transplant kidney biopsies, and pregnancy.
For diabetic patients, renal biopsy was performed in those who were suspected to have renal diseases other than diabetic nephropathy (DN) since renal histology rarely provided further information for the treatment decision in DN.
Each biopsy was performed with an automated biopsy gun with a 16G needle (C Rose Bard Inc®, Murray Hill, NJ, USA). An ATL HDI 5000 ultrasound machine (Philips Medical Systems®, Eindhoven, the Netherlands) was used for localization of the lower pole of the kidney.
All the biopsies were evaluated by LM and IF microscopy; electron microscopy was not available for use in this study. We examined the stained sections using LM; one section was stained with hematoxylin and eosin, one with Periodic Acid-Schiff, one with Masson's trichrome, and one with Jones silver. The IF microscopy panel included IgA, IgM, IgG, C3, C1q, fibrinogen and, if necessary, kappa and lambda light chains.
Histological categories were classified as follows:
- Primary glomerulonephritis (PGN), which included minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), IgM nephropathy (IgMN), mesangioproliferative glomerulonephritis (MesPGN), membranoproliferative glomerulonephritis (MPGN), crescentic glomerulonephritis (CresGN), diffuse proliferative glomerulonephritis (DPGN), and postinfectious glomerulonephritis (PIGN)
- Secondary glomerulonephritis (SGN) included lupus nephritis (LN), DN, amyloidosis (AM), Henoch Schönlein purpura (HSP), light chain deposit disease (LCDD), and systemic vasculitis.
Baseline demographic and biochemical data, including age, gender, history of blood hypertension, degree of proteinuria, serum creatinine, and serum albumin concentration were recorded.
Further analysis was performed by dividing patients into four groups arbitrarily according to age at the time of renal biopsy (15–30, 31–45, 46–60 and >61 years, respectively).
| Statistical Analysis|| |
Statistical analysis was performed by utilizing Statistical Package for Social Sciences (SPSS) version 19.0 for Windows (SPSS Inc., Chicago, IL, USA). Numerical data were expressed as a mean ± standard deviation and categorical data in percentage and numerical values. The Chi square (χ2) test and Fisher's exact test were used to compare qualitative variables. P <0.05 was considered statistically significant.
| Results|| |
Among the 257 patients with NS, 159 (61.9%) were male, 98 (38.1%) were female, with an average age of 40.9 ± 16.7 (range 15–82) years at the time of renal biopsy. One hundred and sixty-six (64.6 %) and 81 (35.4%) patients were diagnosed as primary and SGN, respectively.
The level of albumin was 19.7 ± 7 (range 3–29) g/L, 24 urinary protein excretion was 6.8 ± 3.4 (range 3.5–22) g/24 h, serum creatinine was 22.7 ± 26.8 (range 4–147) mg/L and serum cholesterol was 295 ± 163 mg/dL. One hundred eighty patients (70%) had microscopic or gross hematuria.
The average number of glomeruli was 15.1 ± 8 in each renal biopsy specimen.
MN was the most common underlying cause of NS which was found in 57 (22.2%) cases. MCD was the second most common cause found in 53 (20.6%) cases followed by LN in 35 (13.6%) cases, AM in 34 (13.2%) cases, FSGS in 23 (3.4%) cases, MPGN in 21 (8.2%) cases, DN in 16 (6.2%), IgAN in seven (2.7%) cases, PIGN in five (1.9%) cases, LCDD in four (1.6%) cases each, and HSP in two (0.8%) cases.
The spectrum of NS in different age stratification groups was significantly different (P <0.001). The proportion of patients with LN and MCD decreased in parallel with patient age (P <0.001 and P = 0.006, respectively), and the proportion of patients with renal amyloidosis increased in parallel with patient age (P <0.001) [Table 1].
|Table 1: The histopathological spectrum of patients with nephrotic syndrome at different ages.|
Click here to view
Among the patients between 15 and 30 years old, the most common cause of NS was MCD observed in 25 (32.1%) cases followed by LN observed in 20 (25.6%) cases [Table 1]. Further analysis showed that there was also a significant difference in the diseases spectrum of NS between male and female patients (P <0.001). In male patients, the most common cause of NS was MCD observed in 16 (43.2%) cases, whereas in female patients, the most common cause was LN observed in 17 (41.5%) cases [Table 2]. MCD was still more prevalent in male than in female patients (43.2 vs. 22%, P = 0.04) and LN was still more prevalent in female patients than in male patients (41.5 vs. 8.1 %, P =0.001).
|Table 2: The histopathological spectrum of patients with nephrotic syndrome between different genders.|
Click here to view
Among the patients between 31 and 45 years old, the most common cause of NS was MN observed in 21 (29.6%) cases [Table 1]. In male patients, the most common cause of NS was MN observed in 12 (29.3%) cases, whereas in female patients, the most common cause was LN observed in 11 (36.7%) cases [Table 2]. There was no significant difference in the spectrum of NS between male and female patients (P >0.05). However, LN was still more prevalent in female patients than in male patients (36.7 vs. 2.4%, P<0.001) [Table 2].
Among the patients between 46 and 60 years old, the most common cause of NS was MN and AM observed in 36 (52.2 %) cases [Table 1]. In male patients, the most common cause was MN observed in 14 (28%) cases, whereas in female patients, the most common cause was AM observed in seven (36.8%) cases [Table 2]. There was not a significant difference in the spectrum of NS between male and female patients (P <0.05).
Among the elderly patients (>61 years old), the most common cause of NS was AM observed in 11 (28.2%) cases [Table 1]. In male patients, the most common cause was AM observed in nine (29%) cases, whereas in female patients, the most common cause was MCD and AM observed in four (50%) cases [Table 2] There was no significant difference in the spectrum of NS between male and female patients (P >0.05).
| Discussion|| |
Despite the establishment of national and regional renal biopsy registries, epidemiological data reported from different centers inevitably have geographical, racial, and temporal variations. Furthermore, changing of pattern of glomerulonephritis within the same country probably due to infection control, changing environmental pollution, increased awareness of the disease, and change in the life expectancy.
The disease spectrum of NS has rarely been studied in Moroccan patients. The current study analyzed the renal histopathological spectrum of patients with NS of different ages and genders who underwent a renal biopsy.
Among the 257 patients with NS in our study, the most common pathology was MN (22.2%), followed by MCD (20.6%).This order was similar to that observed in study of China, which involved 1523 patients with NS, reported that MN (20.7%) was the most common cause although its proportion was just 0.3% higher than that of MCD. Similar studies in Spain, Italy, and United Arab Emirates had reported that MN as the leading cause of NS, however, the data were mainly originated from 1990's.,, Therefore we believe that MCD still occupies a significant portion of NS in the recent decades. However, recent studies have found the incidence of FSGS to be gradually increasing worldwide.,,,
IgAN was observed in only 2.7% of all adult patients in our study, this finding is consistent with other studies in India. However, IgAN was the most common type of glomerulopathy in other studies in China.,
Nevertheless, the prevalence of diagnosis did vary with age. MCD was the most common pathology in young adults until the age of 45. Thereafter, AM took the leading position followed by MN [Table 1]. It is also worth to note that AM occurred in 28.2% of cases for patients older than 60 years, with 1.3%, 5.6% and 26.1 in the age 15–30, 31–45 and 46–60 years, respectively. This linear increase of percentage with age was similarly observed in other series.,, Apart from NS, AM may also present as acute kidney injury in 19% of elderly patients according to a subgroups analysis from the Spain Registry. We also found that the proportion of patients with MCD and LN decreased in parallel with patient age, this is in accordance with observations by Zhou et al.
In our study, males were more than females (61.9 vs. 38.1%); this finding is consistent with other studies, and in contrast with others. Our Study showed that MCD were significantly higher in male patients aged 15–30 years old and LN were significantly higher in female patients aged 15–45 years old. This findings was similar to that observed by Zhou et al, in which had a significant difference in the disease spectrum of NS between male and female patients. In male patients aged between 14 and 30 years old, the most common cause of NS was MCD whereas in female patients between aged 14 and 44 LN was the leading cause of NS.
| Limitation of study|| |
There were some biases in the current study. First, our study included a small sample size. Hence, the results may not clearly depict the definite spectrum of glomerular diseases prevalent in adults presenting with NS. Second, in the current study, there were only a few patients with DN, which is one of the most common causes of nephrotic range proteinuria in the elderly. This is because in our center, patients with established diagnosis of DN will not receive renal biopsy since the renal histology will rarely provide further information for the treatment decision.
| Conclusion|| |
The renal histopathological spectrum of NS differs in various age groups. MCD was the main cause of NS among younger patients, and AM were the main cause of NS among older patients. The proportion of patients with AM increased in parallel with patient age. Our study may help to understand the various causes of NS in this region although further studies on a larger population and different geographical locations are warranted for categorization.
Conflict of interest: None declared.
| References|| |
Nishi S, Ubara Y, Utsunomiya Y, et al. Evidence-based clinical practice guidelines for nephrotic syndrome 2014. Clin Exp Nephrol 2016;20:342-70.
Fiorentino M, Bolignano D, Tesar V, et al. Renal biopsy in 2015 From epidemiology to evidence-based indications. Am J Nephrol 2016;43:1-9.
Harris RC, Ismail N. Extrarenal complications of the nephrotic syndrome. Am J Kidney Dis 1994;23:477-97.
Zhou FD, Shen HY, Chen M, et al. The renal histopathological spectrum of patients with nephrotic syndrome: An analysis of 1523 patients in a single Chinese centre. Nephrol Dial Transplant 2011;26:3993-7.
Rivera F, López-Gómez JM, Pérez-García R; Spanish Registry of Glomerulonephritis. Clini copathologic correlations of renal pathology in Spain. Kidney Int 2004;66:898-904.
Schena FP. Survey of the Italian registry of renal biopsies. Frequency of the renal diseases for 7 consecutive years. The Italian group of renal immunopathology. Nephrol Dial Transplant 1997;12:418-26.
Yahya TM, Pingle A, Boobes Y, Pingle S. Analysis of 490 kidney biopsies: Data from the United Arab emirates renal diseases registry. J Nephrol 1998;11:148-50.
Kitiyakara C, Eggers P, Kopp JB. Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States. Am J Kidney Dis 2004;44:815-25.
Bahiense-Oliveira M, Saldanha LB, et al. Primary glomerular diseases in Brazil (19791999): Is the frequency of focal and segmental glomerulosclerosis increasing? Clin Nephrol 2004;61:90-7.
Korbet SM, Genchi RM, Borok RZ, Schwartz MM. The racial prevalence of glomerular lesions in nephrotic adults. Am J Kidney Dis 1996;27:647-51.
Gandra D, Chennamaneni V. Clinico pathological study of nephrotic syndrome in adults. J Evid Based Med Health Care 2015;2:8518-20.
Reshi AR, Bhat MA, Najar MS, et al. Etiological profile of nephrotic syndrome in Kashmir. Indian J Nephrol 2008;18:9-12.
] [Full text]
Zhou FD, Zhao MH, Zou WZ, Liu G, Wang H. The changing spectrum of primary glomerular diseases within 15 years: A survey of 3331 patients in a single Chinese centre. Nephrol Dial Transplant 2009;24:870-6.
Lv J, Zhang H, Zhou Y, et al. Natural history of immunoglobulin A nephropathy and predictive factors of prognosis: A long-term follow up of 204 cases in China. Nephrology (Carlton) 2008;13:242-6.
Jin B, Zeng C, Ge Y, et al. The spectrum of biopsy-proven kidney diseases in elderly Chinese patients. Nephrol Dial Transplant 2014;29:2251-9.
Verde E, Quiroga B, Rivera F, López-Gómez JM. Renal biopsy in very elderly patients: Data from the Spanish registry of glomerulonephritis. Am J Nephrol 2012;35:230-7.
Zainal D, Riduan A, Ismail AM, Norhayati O. Glomerulonephritis in Kelantan, Malaysia: A review of the histological pattern. Southeast Asian J Trop Med Public Health 1995;26:149-53.
Stoycheff N, Stevens LA, Schmid CH, et al. Nephrotic syndrome in diabetic kidney disease: An evaluation and update of the definition. Am J Kidney Dis 2009;54:840-9.
Dr. Yassir Zajjari
Department of Nephrology-Dialysis, Military Hospital Mohammed V, Hay Ryad BP 10100 Rabat
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]