Introduction:
Immunoglobulin Nephropathy (IgAN) is the most common type of primary glomerulonephritis. Up to 40% of patients with IgAN exhibit variable progression to end-stage kidney disease (ESKD) over 10 to 20 years. Previous studies from India report a biopsy prevalence of 4.5%–16%. IgAN is found to be a severe disease with poor outcomes in most Indian studies. Indian patients tend to have greater proteinuria, a higher incidence of kidney failure, and hypertension at the time of presentation. Although there are well-established clinical and histologic risk factors for kidney function decline, when used individually, they are unable to accurately identify high-risk patients. The recent International IgAN prediction tool was developed and tested in a large multiethnic population and integrates both clinical characteristics and the Oxford MEST criteria. This tool allows for 5-year risk prediction of 50% decline in eGFR or progression to kidney failure using data collected at the time of kidney biopsy. A study by Bagchi et al. has validated the tool in Indian cohort; findings have shown reasonably good discrimination of high-risk disease from low and intermediate risk. A recent simulation study has shown that use of this International IgA prediction tool for making treatment decisions (use of immunosuppressive agents) leads to improved outcomes relative to the use of proteinuria alone. The impact of treatment decisions based on the International IgA prediction tool needs to be studied further. Differences in clinical and histological parameters, including prognostic score at the time of biopsy affect treatment response and ultimate short-term and long-term disease outcome. A thorough characterization of these parameters needs to be evaluated.
Methods:
question:
In adult patients diagnosed with biopsy proven IgA Nephropathy: what is the clinocopathological profile and prognostic grade according to International IgA prediction tool at the time of biopsy and treatment outcome during a three month observation period?
B. Research hypothesis:
Individualized treatment decisions based on the International IgA nephropathy prediction tool leads to improved outcomes in patients of IgA nephropathy.
C. Aim and objectives:
Aim:
To comprehensively assess the clinicopathological, prognostic and outcome profile of patients diagnosed with IgA nephropathy using the International IgA prediction tool.
Objectives:
To study the clinicopathological and biochemical profile and prognostic grade according to the International IgA prediction tool at the time of renal biopsy and treatment outcome over a three-month observation period in patients diagnosed with IgA Nephropathy.
D. Study design:
Prospective observational study.
E. Study participants:
All patients who fulfils the inclusion criteria during the study period will be included in the study.
Inclusion criteria:
• Age > 12 years.
• Biopsy-proven IgA Nephropathy: Renal biopsy sample showing at least 6 glomeruli demonstrating dominant or co-dominant deposits of IgA with atleast moderate (2+) positivity on immunofluorescence(IF).
Exclusion criteria:
• Not giving consent.
• Less than 6 glomeruli are available for examination.
• MEST-C score unavailable.
F. Sampling:
Sampling population:
All patients of biopsy proven IgA nephropathy attending the OPD/IPD of Department of Nephrology during the study period will constitute the sample frame for the study.
Sample size calculation:
All patients included in the study.
Sampling technique:
Convenient consecutive sampling.
G. Study procedure:
All patients fulfilling the inclusion criteria will be recruited in the study after informed consent.
Clinical history suggestive of any associated disease which can cause secondary IgA nephropathy will be sought for.
Demographic characteristics and detailed clinical examination.
Patients will be characterized into clinical syndromes.
Biochemical parameters and egfr will be noted.
All patients of primary IgA nephropathy not having progressed to ESKD (egfr<15ml/min/1.73m2), or not having clinical syndrome of AKI/RPRF/Nephrotic syndrome will be evaluated for risk of progression using the International IgA nephropathy prediction tool.
Renal biopsy specimens will be evaluated using the modified OXFORD MEST-C scoring system.
Patients having low and intermediate risk of progression will be treated with supportive measures (salt). restriction, cessation of smoking, ACEI (Ramipril) or ARB (Telmisartan) for optimal BP control to < 130/80 mm Hg, along with SGLT2 inhibitor (Dapagliflozin) as indicated.
Patients having high and highest risk of progression will be treated with oral corticosteroids (Prednisolone 1 mg/kg/day), alongside supportive measures for 3 months as per KDIGO guidelines.
Biochemical parameters, clinical parameters and egfr will be reassessed at the end of 3 months of treatment.
Data will be analyzed for response in clinical and biochemical parameters.
Results:
Herein, we present our interim results.
A total of 27 cases are included.
Male : Female ratio was 1.5: 1.2. Median age of presentation was 24 years (range: 15 to 71 years), most patients were in their second decade (51.85 %).
33% patients presented with unexplained renal failure, 25% presented with rapidly progressive renal failure, followed by nephrotic syndrome (21%), asymptomatic urinary abnormality (17%) and isolated hypertension was noted in 8% patients. 15% patients had macroscopic hematuria and 3 patients were diagnosed with secondary IgA nephropathy. 88% were hypertensive, 5 patients had target organ damage- 2 patients had hypertensive retinopathy along with left ventricular hypertrophy (LVH), 2 patients had isolated retinopathy and 1 patient had LVH.
Among patients who presented with unexplained renal failure, clinically pallor was present in 38%, while edema was present in 50%. Mean systolic BP was 160 mm Hg and mean diastolic BP was 100 mm Hg. Hypertension was present in 100% patients, 1/4th of them had target organ damage. 25% patients received prior treatment with RAAS inhibition.
All patients had highest risk of progression as per International IgAN prediction tool. Mean hemoglobin at presentation was 10.8, creatinine was 2.14, eGFR was 38.54 ml/min, while mean proteinuria was 2.5 gm/day and mean serum albumin was 3.2. Active sediments was present in 88% patients.
100% patients had S1, 62.5% had M1, 50% had T1, while 12.5% had E1 and C1 each; mean IFTA was 22.5%.
37.5% patients received treatment with RAAS inhibition, 62.5% received treatment with combined RAAS inhibition and SGLT2 inhibitor. Except 1 patient all patients received immunosuppression. Overall response was noted in 42.85% with mean improvement in eGFR of 10.33 ml/min and mean proteinuria decline of 1.5 gm/day.
57% patients had progressive disease, with 28.5% patients requiring RRT, despite adequate BP and proteinuria control.
There was no difference in histological parameters and IFTA between the 2 groups.
Patients presenting with asymptomatic urinary abnormalities presented with mean eGFR of 99.75 ml/min and mean proteinuria of 1.4 gm/day. 50% patients had hypertension. 50% patients had intermediate risk of progression while the rest had higher risk of progression. 1 patient was immunosuppressed, showed positive result with eGFR improvement of 26 ml/min.
Patients with Nephrotic syndrome had mean proteinuria of 6.72 g/day, with 20% patients having renal dysfunction and hypertension was noted in 40% patients. 60% patients had complete remission, 20% had partial response while 20% patients had no resopnse.
100% patients presenting with RPRF with mean eGFR of 6.95 ml/min, progressed to end stage kidney disease and were dialysis dependent.
50% patients had side effects of corticosteroid treatment, with most common being proximal muscle weakness.
Conclusions:
International IgAN prediction tool fares well in prognostication of patients with IgA nephropathy. Varying results can be extrapolated from the above findings, stressing on the importance of individualized treatment considerations, keeping in mind the risk-benefit ratio on case to case basis, especially in patients with highest risk of progression. Aggressive immunosuppression didnt fare satisfactorily with respect to preservation of renal function, while on the other hand, increasing the burden of iotrogenic side effects. The reasons behind these findings remain to be elucidated. Further large scale studies are required to validate the above results in larger, generalized population.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.