This was a retrospective, observational study conducted at the Department of Nephrology, Gauhati Medical College and Hospital, Assam, India. We included all adult patients (>18 years of age) who underwent native kidney biopsy in our centre and had CrGN in the biopsy. A total of 80 biopsy-proven CrGN diagnosed from January 2013 to January 2018 were included in this study. Patients with less than seven nonsclerotic glomeruli and no consent were excluded. This study was approved by the institutional ethical committee of Gauhati Medical College and Hospital, and informed consent was obtained from all patients.

Patients’ data regarding demographic profile, clinical features, laboratory parameters, treatments, and morbidity/mortality were collected from the hospital records. Clinical presentations varied from acute kidney injury (AKI), CKD, and asymptomatic urinary abnormalities (AUA). Patients’ outcome data with regard to serum creatinine, development of end-stage renal disease, and complications were collected at each follow-up visit until August 2019.

Hematuria was defined as the presence of ≥5 red blood cells per high power field in urine microscopy. Proteinuria was measured in 24 h timed collection as 24 h urine protein. Serum creatinine was measured by the enzymatic method and estimated glomerular filtration rate was calculated using CKD Epidemiology Collaboration (CKD-EPI) equation (15). AKI was defined as an increase in creatinine level by 0.3 mg/dL (26.5 mmol/L) within 48 h, or a percentage increase in serum creatinine ≥50% (1.5-fold from baseline) within 7 days, or urine volume # 0.5 mL/kg/h for 6 h. CKD was defined as eGFR, 60 mL/min/1.73 m², or markers of kidney damage for more than 3 months (including nephrotic syndrome, AUA, or nephritic syndrome).

Anti-nuclear antibodies (ANA) were measured by indirect IIF assay (catalog number FA 1512-1010-1, Medizinische labordiagnostika, Argentina). Anti-double-stranded DNA antibodies (anti-dsDNA) were measured by enzyme-linked immunosorbent assay (ELISA) (catalog number DNAG37306B BIOGENIX INC. India). Antineutrophil cytoplasmic antibodies (ANCA) were assessed by gauging the anti-myeloperioxidase (anti-MPO) and anti-proteinase 3 (anti-PR3). Anti-MPO (catalog number 704655 Inova Diagnostics, Inc. California, USA) and anti-PR3 (catalog number 704660 Inova Diagnostics, Inc. California, USA) were quantified by the immunoglobulin G (IgG) ELISA kit. Complement factors (C3 and C4) were quantified by nephelometry using antisera (catalog numbers N D08-12 Biocientifica S.A. Argentina and N D09-12 Biocientifica S.A. Argentina respectively).

All kidney biopsy tissue specimens were studied for light microscopy (Magnus opto systems India Pvt Ltd model number CH-20i) and IF microscopy (Zeiss axio zoom v16 model number 3312000226). CrGN was defined by light microscopy as the presence of crescents in more than half of the total glomeruli. IF microscopy was used to categorize the CrGN into types I, II, and III. Type I was characterized by linear deposition of antibodies along GBM and included anti-GBM disease. Type II had granular deposition of immunoglobulins and complement in the glomerulus, and included primary and secondary glomerular diseases. Type III CrGN was defined by the absence of immune deposits in kidney pathology. Interstitial fibrosis and tubular atrophy (IFTA) were graded semiquantitatively into categories none (0), mild (1), moderate (2), and severe (3). Interstitial inflammation was semiquantitatively graded into categories based on the degree of inflammation in tubulointerstitium: 0 (0%), 1 (<20%), 2 (20 to 50%), and 3 (>50%).

Patients were treated as per standard protocols by treating physicians (Table 1). Dialysis was given as indicated. Plasmapheresis was given for patients having severe renal failure (requiring dialysis or serum creatinine >5.7 mg/dL). Patients were followed up with monthly serum creatinine, urine protein, urine microscopy, and blood counts. Patients’ outcomes were collected at the end of follow-up for renal survival, mortality, and eGFR. Multivariate analysis was done to evaluate the risk factors for renal survival.

All data were analyzed using the Statistical software, Statistical Package for the Social Sciences (SPSS v 19.0 IBM Corporation, USA). Continuous data were expressed as mean ± standard deviation or median with interquartile range, and categorical data were expressed as frequencies and percentages. Categorical data were compared by using chi-square test or Fisher’s exact test and continuous data were compared by student’s independent t-test or one-way analysis of variance (ANOVA) test. A five percent level of significance was used to carry the statistical analysis, with a P value of <0.05 being statistically significant.

A total of 1498 kidney biopsies were done in our centre from January 2013 to December 2018, out of which 85 biopsies were having CrGN (5.7%). Three patients were excluded from the study due to inadequate biopsy and two patients had no follow-up data; 80 patients were included in this study. Follow-up duration varied from 3 to 32 months, and more than 1 year of follow-up data were available in 47 patients (58.8%). The etiology of CrGN in our study population is described in Table 1. Type II CrGN was the most common type, followed by type III and type I CrGN. In type II CrGN, lupus nephritis and IgAN were the most common causes of CrGN. The mean age of patients was 40.86 ± 16.5 years. Patients in type III CrGN were older than patients in type I and type II CrGN. Of 80 patients with CrGN, 43 (53.7%) were female and 37 (46.3%) were male. Female predominance was observed in type I and type II CrGN, whereas there was male predominance in type III. Table 2 describes the clinical and laboratory features of our study population. Duration of symptoms was more in type II CrGN than in type I and type III CrGN (P = 0.011). Oliguria was seen in 53.7% of the study population. Skin rash was significantly (P = 0.015) seen more in type II CrGN (38.9%), compared to type I (9.1%) and type III (12.12%). Hemoptysis was seen significantly (0.0432) more in type I (27.3%) and type III (18.2%), compared to type II (2.7%).

Type II CrGN had the highest mean proteinuria (3.9 ± 2.1, P < 0.0001) and lowest mean serum albumin (2.7± 0.7, P = 0.006). The mean estimated glomerular filtration rate (eGFR) was lowest in type I CrGN (6.7 ± 4.9 mL/min/1.73 m²), compared to type II CrGN (16.1 ± 8.6 mL/min/1.73 m²) and type III CrGN (12.4 ± 8.2 mL/min/1.73 m²), with a P value of 0.003. Serum complements were low in around half of the patients (low C3 in 38.7% and low C4 in 12.5%). Complement C3 (P = 0.0001) and C4 (P = 0.01) were significantly lower in type II CrGN, compared to type I and type III CrGN. ANA was positive in 25 cases (31.3%) out of which the majority (72%) belonged to type II CrGN. Anti-dsDNA was positive only in type II CrGN (16 cases, 50%). ANCA positivity was seen in 37 cases (46.3%), the majority of which had type III CrGN. ANCA positivity was seen in 87.9% cases of type III CrGN out of which 54.5% cases had anti-MPO and 39.4% had anti-PR3 autoantibodies. Anti-GBM antibodies were seen in 6% of patients with type III CrGN. In type I CrGN, anti-GBM antibodies were present in 90.1% and ANCAs were present in 18.2% of patients.

Characteristic histopathological features noted in kidney biopsies have been summarized in Table 3. Crescents were seen in 75.1 ± 18.3 of glomeruli with the highest percentage seen in type I CrGN (87 ± 15.2, P = 0.04), followed by type III CrGN (76.4 ± 21.4%) and type II CrGN(70.2 ± 18.1%). Fibrocellular crescents were the most common type of crescent seen in all three groups of CrGN. Mesangial proliferation (69.4%, P = 0.0005) and endocapillary proliferation (97.2%, P ≤ 0.0001) were mostly seen in type II CrGN. The highest percentage of glomeruli with neutrophilic infiltrates was seen in type I (81.2%, P = 0.00861), followed by type II (52.7%) and type III (30.3%) CrGN. Tuft necrosis was significantly seen more in type I CrGN and type III CrGN (45.5% and 24.2%, respectively, P = 0.01937), compared to type II CrGN (8.3%). Chronic lesions in the form of moderate/severe IFTA were seen more in type I CrGN (63.6%), although not statistically significant.

Treatments of the patients were done as per the standard guidelines (16). Table 4 describes the treatment received by the patients in this study. Hemodialysis was needed in more than half of the cases at the time of presentation and was significantly more common in type I (72.7%) and type II (57.6%) CrGN (P = 0.0034). Immunosuppression was given in 88.7% of the patients with no difference between the three groups of CrGN. The majority of patients received steroids plus cyclophosphamide, while 21.2% of patients received steroids alone. Fourteen patients (21.25%) received therapeutic plasma exchange, which was significantly (P = 0.0046) more in type I CrGN (45.5%) and type III CrGN (30.3%), compared to type II CrGN (5.6%).

Patients were followed up with a mean follow-up of 23.1 ± 12.4 months. Table 5 describes the outcomes of our study population. Death, renal survival, and eGFR at the end of follow-up were assessed for the outcome of our study population. At the last follow-up, the mean eGFR was 25.8 ± 11.41 mL/min/1.73 m² and was significantly lower in type I CrGN (11.6 ± 4.8 mL/min/1.73 m²). Renal survival at the end of follow-up was seen in almost half of the patients. Patients with type III CrGN (48.5%) and type II CrGN (69.5%) had significantly better renal survival, compared to type I CrGN (27.3%, P = 0.0299). The overall mortality was 7.5% and there was no significant difference among the three types of CrGN. We analyzed the risk factors of poor renal outcome (Table 6). In our study, oliguria at the time of presentation, a higher percentage of crescents, glomerular sclerosis, and moderate/severe IFTA were associated with poor renal outcomes.