Acute kidney injury (AKI) is a prevalent and clinically important syndrome with the emergence of an acute loss of kidney function, which is determined by modern practice based on the alterations in serum creatinine and/or urine output by the kidney disease: Improving Global Outcomes (KDIGO) classification [1]. Long hospital stays, high health-care expenses, renal replacement therapy, and a significant increase in the short-term mortality are all linked to AKI, making it one of the highest priority complications among hospitalized patients across the globe [2]. Its burden is especially significant in low- and middle-income countries, where delayed diagnosis, lack of access to nephrology services, and dialysis access can be thought of as causes of avoidable morbidity and mortality [3].

In addition to its short-term effect, AKI is currently considered to be a significant predictor of long-term renal outcomes. Even with apparent short-term recovery, patients who experience an episode of AKI are still susceptible to chronic kidney disease (CKD), end-stage kidney disease and lower long-term survival [4]. This has highlighted the need to diagnose etiology early and correctly risk stratify patients with AKI.

Not a single disease entity, AKI is a heterogeneous clinical syndrome caused by a variety of prerenal, intrinsic renal, and postrenal causes. The pathology spectrum of intrinsic renal causes covers a wide range and includes acute tubular injury, acute interstitial nephritis, crescentic glomerulonephritis, immune-complex mediated glomerular disease, thrombotic microangiopathy, cortical necrosis, and paraprotein-related renal injury [5]. Due to the similarity in clinical and biochemical appearance of these lesions, clinical examination and regular laboratory studies alone might not necessarily determine the exact underlying pathology.

Renal biopsy is still the gold standard in making tissue diagnosis in the selected patients with unexplained, severe or atypical AKI [6]. Histopathology aids in distinguishing between tubular, interstitial, glomerular, and vascular etiologies of AKI and therefore enhances the diagnosis, disease-specific treatment, and offers valuable prognostic data [6]. Whereas kidney biopsy is an invasive method, the evidence available indicates that kidney biopsy is highly diagnostic with reasonably good safety profile in the majority of patients when done with the proper precautions and ultrasound guidance [7].

Although the diagnostic importance of renal biopsy is realized, there is lack of prospective clinicopathological data on biopsy-proven AKI and frequency of particular lesions might be different based on local disease epidemiology, referral patterns, and comorbidity burden. Comparison of histopathological observations with clinical presentation and laboratory parameters could enhance the insight into disease trends, help to identify potentially curable lesions at an early stage, and clarify the prognostic consequences. Thus, the current work was done to assess the histopathological range of the renal biopsy results in AKI patients and to compare the results with the clinical and laboratory context.

AIM

To evaluate the histopathological patterns of renal biopsy in patients with acute kidney injury and to correlate these findings with their clinical and laboratory profile.

OBJECTIVES

1. To study the spectrum of histopathological changes observed in renal biopsy specimens of patients diagnosed with acute kidney injury.
2. To correlate renal biopsy findings with clinical presentation and laboratory parameters such as serum creatinine, blood urea, urine examination, electrolyte abnormalities, and other relevant investigations.
3. To assess the diagnostic and prognostic value of renal biopsy in identifying the underlying etiology and guiding management in patients with acute kidney injury.

Study design and setting

This prospective, observational, hospital-based study was conducted over a period of 10 Month, from January 2025 to Oct 2025, at Malati multispeciality hospital and medical college, Khurd, Akola, Maharashtra, involving the Departments of Medicine, and Pathology.

Study population

The study included adult patients admitted with acute kidney injury (AKI) who underwent native renal biopsy as part of diagnostic evaluation during the study period. A total of 100 consecutive eligible patients were enrolled.

Inclusion criteria

Patients were included if they fulfilled all of the following criteria:

1. Age more than 18 years.
2. Diagnosis of AKI based on clinical and biochemical parameters.
3. Admission to Malati Multispeciality Hospital and Medical College during the study period.
4. Renal biopsy indicated and performed as part of diagnostic evaluation.
5. Written informed consent provided for participation and renal biopsy.

Exclusion criteria

Patients were excluded if they had any of the following:

1. Known chronic kidney disease or bilaterally shrunken kidneys suggestive of chronic irreversible renal disease.
2. Contraindications to renal biopsy, including bleeding diathesis, uncontrolled hypertension, solitary kidney, severe anemia, or uncorrected coagulation abnormalities.
3. Hemodynamic instability precluding renal biopsy.
4. Inadequate or inconclusive biopsy specimen.
5. Refusal to provide written informed consent.

Clinical and laboratory assessment

All patients underwent detailed clinical evaluation at the time of admission, including history taking, physical examination, and laboratory investigations. Baseline demographic data including age and sex were recorded. Clinical variables documented included oliguria, edema, gross hematuria, hypertension, diabetes mellitus, coronary artery disease, and clinical sepsis. Other relevant systemic manifestations were also noted wherever present.

Baseline laboratory investigations included complete blood count, serum creatinine, blood urea, serum sodium, serum potassium, serum bicarbonate, C-reactive protein, and urine routine microscopy. Urinary abnormalities including proteinuria, hematuria, and pyuria were recorded. Proteinuria was assessed by 24-hour urinary protein estimation or spot urine protein estimation, depending on clinical feasibility. Ultrasonography of the abdomen and kidneys was performed prior to biopsy in all patients. Additional serological investigations were performed wherever clinically indicated.

The severity of AKI at presentation was classified according to Kidney Disease: Improving Global Outcomes (KDIGO) staging into stage 1, stage 2, and stage 3 based on standard criteria.

Renal biopsy and histopathological evaluation

Renal biopsy was performed under aseptic precautions and ultrasound guidance after obtaining written informed consent. Biopsy specimens were processed and examined in the Department of Pathology. Histopathological diagnosis was established on the basis of the predominant lesion pattern.

The final histopathological diagnoses included acute tubular injury/necrosis, crescentic glomerulonephritis/rapidly progressive glomerulonephritis, immune complex glomerulonephritis, acute interstitial nephritis, thrombotic microangiopathy, lupus nephritis, myeloma cast nephropathy, diabetic nephropathy with superimposed AKI, obstructive/pyelonephritis-related tubulointerstitial injury, and acute cortical necrosis.

For clinicopathological correlation, biopsy findings were additionally grouped into three broader pathological categories:

1. Glomerular-predominant lesions
2. Tubulointerstitial-predominant lesions
3. Other/vascular-metabolic lesions

Clinicopathological correlation

Clinical, biochemical, and histopathological data were correlated to determine the spectrum of renal lesions in AKI and their relationship with presenting clinical and laboratory parameters. Particular attention was given to the association between pathology group and oliguria, edema, gross hematuria, serum creatinine, blood urea, proteinuria, hematuria, pyuria, and dialysis requirement.

Treatment and follow-up

Management decisions after biopsy were recorded, including initiation of steroids, immunosuppressive therapy, plasmapheresis, and requirement for dialysis. Patients were followed for a period of 3 months after diagnosis. Outcome at 3 months was categorized as complete recovery, partial recovery, no recovery/progression to chronic kidney disease, or death. Three-month serum creatinine was also recorded in surviving patients.

Data collection

Data were collected using a predesigned and pretested proforma. The following information was documented:

1. Demographic details
2. Comorbidities
3. Clinical presentation and examination findings
4. Baseline laboratory parameters
5. Imaging findings
6. Histopathological diagnosis on renal biopsy
7. Grouped pathological category
8. Biopsy-guided treatment instituted
9. Dialysis requirement
10. Short-term outcome at 3 months
11. Three-month serum creatinine

Outcome measures

The primary outcome measure was the spectrum of histopathological lesions detected on renal biopsy in patients with AKI.

Secondary outcome measures were:

1. Correlation of histopathological findings with clinical presentation
2. Correlation of histopathological findings with laboratory parameters
3. Requirement for dialysis
4. Biopsy-guided therapeutic intervention
5. Short-term renal outcome at 3 months
6. Three-month serum creatinine according to histopathological diagnosis

Statistical analysis

Data were entered into Microsoft Excel and analyzed using appropriate statistical software. Quantitative variables were expressed as mean ± standard deviation or median with interquartile range, as appropriate, and qualitative variables as frequency and percentage. Comparisons between pathology groups were performed using the chi-square test for categorical variables, one-way analysis of variance (ANOVA) for normally distributed continuous variables, and Kruskal-Wallis test for non-normally distributed continuous variables. A p-value <0.05 was considered statistically significant.

Ethical considerations

The study was conducted after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participants before inclusion in the study and prior to performance of renal biopsy.

Baseline clinical and laboratory profile

A total of 100 patients with acute kidney injury who underwent renal biopsy were included in the analysis. The mean age of the cohort was 45.83 ± 13.53 years, and 54.0% were male. Hypertension and diabetes mellitus were present in 40.0% and 28.0% of patients, respectively. Oliguria was the most frequent presenting feature (49.0%), followed by edema (28.0%) and gross hematuria (15.0%). At presentation, 30.0% of patients had KDIGO stage 1 AKI, 44.0% had stage 2 AKI, and 26.0% had stage 3 AKI. The mean serum creatinine and blood urea were 4.06 ± 1.08 mg/dL and 95.67 ± 27.57 mg/dL, respectively (Table 1).

Table 1. Baseline clinical and laboratory profile of the study cohort

Values are mean ± SD, median (IQR), or n (%), as appropriate.

 Spectrum of histopathological diagnoses

Renal biopsy demonstrated a broad spectrum of histopathological lesions. The most frequent diagnosis was acute tubular injury/necrosis (29.0%), followed by crescentic glomerulonephritis/rapidly progressive glomerulonephritis (13.0%), immune complex glomerulonephritis (11.0%), acute interstitial nephritis (11.0%), and thrombotic microangiopathy (10.0%). Taken together, tubulointerstitial-predominant lesions accounted for 44.0% of biopsies, glomerular-predominant lesions for 31.0%, and other vascular/metabolic patterns for 25.0% (Table 2, Figure 1).

Table 2. Spectrum of histopathological diagnoses on renal biopsy in AKI

 Clinicopathological correlation

Biopsy pattern showed significant correlation with several laboratory parameters. Patients with glomerular-predominant lesions had substantially higher proteinuria and hematuria than those with tubulointerstitial or other vascular/metabolic lesions (both p < 0.001). Blood urea levels also differed significantly among pathology groups (p = 0.010), with the highest mean values observed in the other/vascular-metabolic group. Pyuria tended to be more prominent in tubulointerstitial lesions, although this did not reach statistical significance (p = 0.055). Serum creatinine, oliguria, edema, gross hematuria, and dialysis requirement did not differ significantly across pathology groups (all p > 0.05) (Table 3).

 Table 3. Correlation of pathology group with key clinical and laboratory parameters

Continuous variables are shown as mean ± SD or median (IQR), as appropriate. p values derived from ANOVA, Kruskal-Wallis, or chi-square tests.

 Diagnostic and prognostic value of renal biopsy

Renal biopsy findings influenced subsequent management in a substantial proportion of patients. Steroids were initiated in 36.0% of cases, immunosuppression in 26.0%, and plasmapheresis in 4.0%, reflecting biopsy-confirmed treatable immune-mediated disease. Overall, 36.0% of patients required dialysis. At 3 months, 37.0% achieved complete recovery, 41.0% had partial recovery, 18.0% showed no recovery or progression to chronic kidney disease, and 4.0% died in hospital (Table 4).

Table 4. Biopsy-guided management and short-term outcomes in the overall cohort

Outcome according to histopathological diagnosis

Short-term outcome varied significantly according to histopathological diagnosis (p = 0.003). Complete recovery was most frequent in immune complex glomerulonephritis (72.7%) and obstructive/pyelonephritis-related tubulointerstitial injury (50.0%), whereas no recovery or CKD progression predominated in acute cortical necrosis (75.0%) and myeloma cast nephropathy (33.3%). All four in-hospital deaths occurred in patients with severe intrinsic renal pathology, including acute cortical necrosis, crescentic glomerulonephritis, and thrombotic microangiopathy. Three-month serum creatinine also differed significantly across histopathological categories (ANOVA p = 0.013), being highest in acute cortical necrosis and myeloma cast nephropathy (Table 5, Figure 2).

Table 5. Three-month outcome according to renal biopsy diagnosis

Outcome distribution across histopathological diagnoses: chi-square p = 0.003. Three-month serum creatinine excludes patients who died in hospital.

The current article emphasizes the heterogeneity of biopsy-proven AKI, where acute tubular injury/necrosis (29%) came out as the most common injury, followed by crescentic glomerulonephritis, immune complex glomerululonephritis, acute interstitial nephritis, and thrombotic microangiopathy. This trend is generally consistent with biopsy-based AKI series demonstrating that when patients with unexplained or severe intrinsic AKI are chosen to undergo tissue diagnosis, the spectrum of lesions extends far beyond nonspecific tubular damage and contains a significant percentage of potentially curable glomerular and interstitial disorders. A significant portion of biopsy-proven AKI patients was associated with vasculitis, acute interstitial nephritis, and crescentic glomerulonephritis in the Spanish Registry analysis by Lopez-Gomez et al., consistent with the importance of biopsy in etiological stratification of AKI patients selected [8]. Our slightly increased percentage of ATI/ATN is probably due to local referral and biopsy selection in patients with atypical or severe AKI in the absence of an apparent pre-biopsy diagnosis.

Our cohort revealed an important observation, namely, that glomerular-predominant lesions were not only characterized by urinary abnormalities much more than by increased azotemia at presentation, but also there was a significant reduction in the rate of these lesions. The difference between proteinuria and hematuria was significantly more pronounced between pathology groups (all p<0.001), but not was the case with serum creatinine and oliguria. This implies that active urinary sediment, in biopsy-selected AKI, might be a more effective localization of pathology compared to creatinine severity alone. This is confirmed by histopathology based studies of Kudose et al., who have shown that clinical severity of AKI and the underlying lesion pattern do not always correlate linearly, highlighting the shortcomings of using biochemical severity to conclude about pathology [9]. Therefore, in patients with AKI and disproportionate hematuria or proteinuria, biopsy can be particularly diagnostic, identifying a crescentic glomerular disease or immune-mediated glomerular disease that needs specific treatment.

Our study is also interested in the outcome profile of acute interstitial nephritis. AIN represented 11% of biopsies with full recovery of 45.5% and none with recovery or CKD progression at 3 months. This pattern of intermediate outcomes is similar to previous biopsy-proven AIN cohorts, in which renal recovery is frequently incomplete despite therapy. Muriithi et al. have discovered that biopsy-proven AIN is often drug-related and also that the reversibility can vary, whereas Prendecki et al. have discovered some better renal outcomes in steroid-treated patients, which might change the prognosis with timely identification and interventions [10,11]. We may thus conclude that biopsy is particularly useful in the suspected AIN, not only to make the diagnosis but to determine a subgroup where previous disease-specific therapy can be used to preserve kidney function.

The worse renal results on the vascular and metabolic lesions were also in agreement with the published experience. Thrombotic microangiopathy was the most dialysis intensive (70%), and acute cortical necrosis demonstrated the worst recovery profile with 75 percent progressing to no recovery/CKD. The biological explanation of these findings is that both lesions indicate severe microvascular and ischemic damages with little or no reversibility once they occur. Previous literature reported cortical necrosis as a ravaging type of AKI that is not salvaged by renal mechanisms, especially in developing-country contexts [12]. Likewise, studies of biopsy-proven renal TMA have shown that it is associated with more severe renal injury and adverse renal outcomes, especially when occurring in the context of systemic immune-mediated disease [13]. Our findings align with this negative prognostic trend and indicate that biopsy confirmation in this type of lesions has specific prognostic importance even in the case of limited therapeutic choices.

The prognostic value of biopsy is further supported by the lesion-specific short-term outcomes in the case of lupus nephritis and myeloma cast nephropathy. Full recovery was rare in our cohort with active lupus nephritis and was not the case in myeloma cast nephropathy, but non-healing dysfunction was common. More recent clinicopathologic research has also demonstrated that AKI overlaid on lupus nephritis is linked to worse renal outcomes, particularly in later stages of AKI [14]. In the case of cast nephropathy, the recent series still indicate that the renal recovery is strongly determined by the early hematologic response, and the intensity of tubular cast load, and a significant proportion of patients do not restore their baseline renal function [15]. Based on this, the low performance in these categories in our cohort seems to be due to lesion biology, rather than center-specific variation.

One of the clinical implications of the current study is that renal biopsy was not simply confirmatory, but had management implications. Steroids were initiated in 36% of the patients, immunosuppression in 26% and plasmapheresis in 4% which means that tissue diagnosis changed treatment in significant percentage of cases. This treatment response is consistent with the biopsy-based AKI literature that points to the fact that histological diagnosis is the most useful in the subset where supportive care would be inadequate or unsuitable alone [8,9]. On the whole, our results endorse a selective yet proactive biopsy method in AKI patients who have a positive urinary sediment, that is not explained, or is suspected of an immune-mediated, interstitial, vascular, or paraprotein-related disease.

Limitation

This was a single-center study with a relatively small sample size and included only patients who underwent renal biopsy; therefore, the findings may not be generalizable to all AKI patients. In addition, the short follow-up period limited assessment of long-term renal outcomes.

Renal biopsy in selected patients with AKI revealed a wide spectrum of underlying lesions, with acute tubular injury/necrosis being the most common, while glomerular, interstitial, and vascular lesions contributed substantially to disease burden. Urinary abnormalities, particularly proteinuria and hematuria, showed better clinicopathological correlation than serum creatinine alone. Renal biopsy also had important therapeutic and prognostic value by identifying treatable lesions and helping predict short-term renal outcome.

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