IGA NEPHROPATHY CLINICOPATHOLOGICAL ASSOCIATION WITH MEST-C SCORING

Introduction:

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. IgAN occurs in individuals of all ages, but it is more common in the 2nd and 3rd decades of life and is much more common in males than females. The prevalence as well as the prognosis of IgAN shows geographic and ethnic variation. It is reported to be significantly more common in Asians and known to have an aggressive course in Asians.

Patients may present with various clinical syndrome ranging from asymptomatic urinary abnormalities to rapidly progressive glomerulonephritis to chronic kidney disease (CKD). Up to 20-40% of patients with IgAN progress to ESKD within 10-20 years after diagnosis.

Clinical course of disease is heterogeneous and the risk of progression to End Stage Kidney Disease (ESKD) can be predicted using Oxford MEST scoring and prognosticated using International IgA nephropathy prediction tool. The Oxford classification of IgAN developed in 2009 provides a histopathological grading system based on four variables: (1) mesangial hypercellularity (M); (2) endocapillary hypercellularity (E); (3) segmental glomerulosclerosis (S); (4) tubular atrophy/interstitial fibrosis (T). Crescents (C) was later included in the revised 2016 Oxford classification called MEST-C scoring

M, S and T were three features which independently predicted outcome and provided prognostic information in addition to prognostic prediction given by clinical features alone. T score largely reflects the stage of disease at the time of biopsy; those patients with more advanced chronic damage have a shorter time to ESKD. Among patients with E, rate of renal function decline was significantly lower in those recieving immunosuppression therapy. E is predictive of outcome, but only in those without immunosuppression.

MEST-C scoring has been evaluated in multiple population cohorts, but there is a paucity of data among Indians. The original Oxford cohort also did not include Indian patients. In this study, we attempt to analyze the clinical and pathological profile and kidney outcome and patient outcome of patients with IgAN diagnosed and managed in our centre, a tertiary care Hospital in South India

Methods:

Materials: Electronic medical records under HMIS (Health management information system)

Study type: Retrospective observational study

Study population and period of study: Patients who had undergone renal biopsy in NU hospitals, Bengaluru between 1st April 2014 and 31st March 2024 and were diagnosed with primary IgAN

Patients below 18 years of age were excluded from the study

We collected the following data on the clinical and laboratory profile of the patients diagnosed with primary IgAN from the electronic medical records at presentation: age, gender, presence of diabetes mellitus and hypertension (detected prior to presentation or at presentation), presence (and duration if present) of symptoms (hematuria, frothy urine, edema, reduced urine output); proteinuria, microscopic hematuria, serum creatinine and eGFR at presentation. Nephrotic range proteinuria was defined as urine spot protein creatinine ratio more than >3.5 or urine protein on dipstick >3+. Microscopic hematuria was defined as presence of ≥5 Red blood cells/high power field on urine microscopy. Estimated GFR was calculated based on CKD EPI creatinine 2021 equation and expressed in ml/minute/1.73m2. Patients were grouped using eGFR values into those with eGFR (in ml/minute/1.73m2) ≥60, those with eGFR 30 to 59 and those with eGFR <30. Renal deterioration was defined as ≥ 50% decline in eGFR or ESKD.

Histopathology was reported by Renal Pathology Consultant. The MEST-C score assigned as per the Oxford classification and reported by nephropathologist was tabulated. Presence or absence of crescents as mentioned in the reports was recorded for patients who were biopsied before 2017. Additional biopsy findings in both native and graft kidney biopsies were recorded.

Follow up was censored at death or initiation of renal replacement therapy whichever was the first event. The patients alive and not on renal replacement therapy were followed up and data on proteinuria and eGFR on the day of last follow up and use of Angiotensin converting enzyme inhibitors (ACEi) or Angiotensin receptor blockers (ARBs) and details of immunosuppression given were also collected. Management protocol focussed on optimum control of blood pressure and use of ACEi or ARB; Immunosuppression and steroid use were considered as per KDIGO guidelines.

Results:

146 biopsies in 145 patients (one renal allograft recipient had undergone graft biopsy twice; the repeat biopsy done 47 months after the first one was indicated by rapid decline in eGFR and worsening of proteinuria) were diagnosed with primary IgAN out of 896 renal biopsies performed during the study period at NU hospitals, Bengaluru and met our inclusion criteria. It included 128 native kidney biopsies (87.67%) and 18 allograft kidney biopsies (12.32%).

Table 1 shows the baseline clinical and laboratory profile of these patients at the time of biopsy. The patients were predominantly male (76.02%). Mean age at the time of biopsy (±standard deviation) was 42.18 (±14.14) years (range 18 to 82 years). Diabetes mellitus was present in 42 (28.76%), Hypertension prior to presentation, in 100 (68.49%) and Hypertension at presentation in 29 (19.86%) patients.

Nearly a third [53 (36.3%)] of biopsies followed incidental detection of evidence of kidney disease during evaluation for hypertension or regular screening for coexisting illness (diabetes mellitus) or transplant follow up or in the setting of intercurrent illness (fever, stones etc). Microscopic hematuria was observed in 35 (23.97% of total) and proteinuria in [nephrotic range in 20 (13.69% of total)]. Microscopic hematuria was observed in association with nephrotic range proteinuria in 14 (9.58%).

Patients who presented with one or other symptom of edema, red urine, reduced urine output and frothy urine had a median duration of symptoms of 29 days prior to presentation (range from as early as 2 to as late as 1038 days prior to presentation).

Overall 143 (97.9%) patients had proteinuria and 102 (69.86%) patients had microscopic hematuria. 64 (43.83%) patients had nephrotic range proteinuria.

75 (51.36%) patients presented with eGFR <30 ml/min/1.73m2 at the time of biopsy. 31 (21.23%) patients required dialysis at the time of biopsy. Closer to 50% [15 (10.27% of total)] patients were advised continuation on dialysis after biopsy in view of uremia, biopsy findings and the absence of obvious reversible factor and were censored from analysis on outcome

The remaining 130 (89.72%) were followed up over a median duration of 30 months (range 0 and 122 months). 51 (38.93%) patients reached ESRD during follow up of which 33 (25.19%) patients were started on dialysis in our Hospital. 2 (1,52%) patients with ESKD died during the follow up period.

21 (16.03%) patients excluding renal transplant recipients received steroids and 7 (5.34%) patients among them also received immunosuppression therapy as they had cresentic transformation on biopsy.

Table 2 shows kidney outcome in patients who received ACEi/ARBs during follow up. 68 (51.9%) patients received ACEi/ARBs during follow up. 27 (39.7% of total) patients had eGFR ≥60 at presentation and 25 (36.76% of total) patients had preserved eGFR ≥60 during the follow up period. 22 (32.35% of total) patients had nephrotic range proteinuria at presentation while only 2 (2.94% of total) patients had nephrotic range proteinuria at last visit.

Table 3 shows the distribution of MEST-C lesions in 131 patients who continued follow up. 80 patients had adequate biopsy sample with ≥8 glomeruli without advanced sclerosis. Sclerosis and mesangial hypercellularity were the most common lesions observed on histopathology. Severe tubular injury and associated crescents were observed in one eighth. Among 31 patients who had nephrotic proteinuria in this sub group, 25 (80.64%) had M or S score of 1; those patients with T score of 1 or 2 had more advanced kidney disease at the time of presentation with more chances of progressing to ESRD as compared to others with T score of zero. Patients who progressed to ESRD at follow up had S1 or T1/2 which made up 66.67% of ESRD patients in this group. 70.83% of patients who progressed to ESRD at follow up had M1 score.

Chart 1 depicts additional biopsy findings in native kidney biopsies; 11 patients had Diabetic nephropathy, 2 had malignant nephrosclerosis, 2 had acute tubular injury, 1 patient had amyloidosis, 1 patient had Focal segmental glomerulosclerosis, 1 patient had acute interstitial nephritis, 1 patient had pyelonephritis and 1 patient had chronic interstitial nephritis.

5 patients with IgAN with crescents required continuation of dialysis from the time of presentation and 3 patients required dialysis start during follow up. 2 patients with Diabetic nephropathy required continuation of dialysis from the time of presentation and 3 required dialysis start during follow up.

Chart 2 depicts additional biopsy findings in graft kidney biopsies of which 4 patients had Antibody mediated rejection, 4 had Cell mediated rejection, 2 had IgAN with crescent and 1 had Plasma cell rich rejection. All patients with IgAN with crescent and Plasma cell rich rejection landed up on RRT at follow up.

Conclusions:

1. Significant proportion of patients were incidentally detected to have IgAN during evaluation or routine screening of other clinical conditions.
2. Around two fifth of patients had nephrotic proteinuria and one half had eGFR less than 30 ml/min/1.73m2 at presentation.
3. ACEi or ARB was used only in 52% of patients during follow up; this figure needs improvement.
4. 0.78 events occurred per 100 patient years.
5. Follow up percentage is low and efforts need to be made to improve follow up.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.