Renal Papillary Necrosis Identified by Native Kidney Biopsy: Insights Beyond Radiology

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Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary papillae and pyramids.¹ Many etiologic factors have been associated with pathogenesis.² RPN can be identified through several imaging modalities.³ Our study describes the clinicopathologic features of RPN based on a series of native kidney biopsies diagnosed at our center between August 2013 and June 2025.

A 65-year-old male presented with gross hematuria and impaired renal function. He had no known comorbidities. Initial investigations revealed a serum creatinine of 12 mg/dL and 3+ proteinuria. Complete blood counts, viral markers, and serum electrolytes were within normal limits. Urine culture was negative for microbial growth, and abdominal ultrasound showed no abnormalities. Renal biopsy was performed to determine the underlying cause. The immunofluorescence study of the routine antisera panel was negative. Light microscopy revealed coagulative necrosis of the deep medullary tissue, with the cortex and superficial medulla remaining viable [Figure 1a-b]. Additionally, there were features of acute pyelonephritis, characterized by neutrophilic tubulitis and pus cell casts within the tubular lumina of the viable medulla. Following conservative management with antibiotics, the patient’s hematuria resolved, and renal function normalized. This case highlights the uncommon early diagnosis of RPN by histopathology rather than the usual radiological diagnosis. This prompted us to perform a retrospective analysis of RPN cases from our database.

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Figure 1:

(a) Coagulative necrosis of the renal papilla (orange arrow). Note that the cortex and major portion of medulla in this biopsy are viable. Hematoxylin& eosin (H&E) 4X. (b) There is loss of cellular definition, with preserved tubule outlines (ghost tubules). H&E 10X. (c) Within the necrotic renal papillae, there are Periodic acid Schiff (PAS) positive, encapsulated, round to oval, variably sized yeast forms (yellow arrows) consistent with Cryptococcus species. PAS 40X.

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Nineteen native kidney biopsies were diagnosed with RPN during the study period. The mean age of the patients was 55.7 ± 11.9 years (range: 2 months to 75 years). The cohort included 11 males and eight females. At the time of biopsy, the clinical presentation included AKI (63.1%), rapidly progressive renal failure (21%), and acute worsening of CKD (15.7%). The mean serum creatinine was 5.8 ± 3.4 mg/dL. The degree of proteinuria varied: trace in two, 1+ in four, 2+ in seven, and 3+ in two patients, while data were unavailable for the remaining cases. Urine cultures were negative in four patients, and culture results were unavailable for the others. Comorbidities included diabetes mellitus (47.3%), hypertension (52.6%), coronary artery disease (10.5%), chronic calcific pancreatitis (5.2%), and Diamond-Blackfan anemia (5.2%). Additional clinical data, available in a subset of patients, indicated bacterial sepsis in two cases, Candida sepsis in one, urinary tract infection in one, NSAID use in three, and snakebite in one patient. Notably, ultrasound imaging was reported as normal in all cases. Pathological examination demonstrated coagulative necrosis of the renal medulla in all cases, with preservation of the cortical tissue [Figure 1]. Notably, eight biopsies (42.1%) showed features of diabetic nephropathy, either alone or in combination with tubulointerstitial changes. An underlying infectious etiology was identified in seven biopsies, including acute pyelonephritis in six cases (31.5%), and cryptococcal infection in one case (5.2%). Additionally, seven biopsies exhibited tubulointerstitial pathology, consisting of acute tubular injury (3/7), acute interstitial nephritis (3/7), and chronic tubulointerstitial nephritis (1/7).

RPN is characterized by necrosis of the renal medullary papillae and pyramids. The hallmark coagulative necrosis observed in biopsy specimens suggests ischemic infarction as the underlying mechanism. Ischemia may result from disturbances in renal blood flow or prolonged hypotensive episodes. The vasa recta, which supply the papillae, originate at the base of the renal pyramids and progressively narrow toward the apex and papillary tip. This unique anatomical feature renders the papillae particularly vulnerable to ischemic injury and oxidative stress.¹ Early diagnosis and identification of the underlying etiology are essential to prevent potentially fatal complications. Necrotic papillae can slough off and obstruct the ureter, presenting as renal colic and leading to rapid deterioration of renal function.² In these cases, timely removal of the obstructing necrotic tissue, combined with targeted treatment of the underlying cause, is crucial for patient recovery. CT urography is the preferred imaging modality for diagnosing RPN, but it was not performed in any of the patients due to impaired renal function. Although all patients underwent ultrasound examination prior to biopsy, none were radiologically diagnosed with RPN. Histological analysis revealed early-stage RPN in all cases, with necrotic papillary tips remaining attached to the medulla, rather than sloughed papillae typically seen in advanced disease. This finding highlights the low sensitivity of ultrasound for detecting early RPN, where imaging findings may be normal.³ The subtle, and often nonspecific clinical features of renal RPN have been documented in biopsy, nephrectomy, or autopsy specimens.^4-6 Though often asymptomatic, RPN should be considered when patients present with fever, chills, flank or abdominal pain, hematuria, or persistent urinary tract infections despite negative imaging. RPN should be suspected in patients with risk factors like analgesic abuse, sickle cell disease, diabetes, urinary obstruction, pyelonephritis, tuberculosis, or renal vein thrombosis.⁷ Infection was the most common cause of RPN in our series. RPN related to acute pyelonephritis, especially in diabetics, likely results from vascular compression by inflammatory exudates.⁶ Diabetes mellitus was present in 47.3% of patients. Acute pyelonephritis was confirmed on biopsy in two diabetic and four non-diabetic patients. Cryptococcal pyelonephritis, identified by PAS-positive yeasts in renal tissue as seen in our case [Figure 1c], has also been described by Randall et al.⁸ The biopsy additionally showed features of diabetic nephropathy. Urine culture for Cryptococcus was negative; this is consistent with the rarity of isolating Cryptococcus in routine urine cultures, which are typically positive only in disseminated disease, high fungal burden, or marked immunosuppression.⁹ Analgesic use, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), may contribute to RPN by inhibiting prostaglandin synthesis, leading to medullary vasoconstriction and ischemia.² Discontinuing the offending agent is an effective intervention. Three patients reported NSAID use prior to renal injury; medication history was unavailable for the others. Snake envenomation can cause diverse renal lesions such as acute tubular injury, interstitial nephritis, cortical necrosis, and thrombotic microangiopathy. RPN with cortical sparing, observed in one patient, is uncommon and may be the result of hemolysis, rhabdomyolysis, or direct nephrotoxic effects of the venom.¹⁰

RPN is often an incidental finding in native kidney biopsies performed for unexplained renal failure. Infections, particularly acute pyelonephritis, were the most common underlying etiology in our series, with diabetic nephropathy as the predominant glomerular pathology. Our findings underscore the importance of considering RPN in patients with unexplained renal dysfunction, especially when associated with risk factors such as diabetes, infections, or analgesic use. Histological evaluation plays a crucial role in detecting early-stage RPN, which may be missed on imaging. Due to the retrospective design of our study, treatment details and long-term outcomes were limited. The absence of standardized imaging protocols, such as CT urography, hindered reliable radiological-histopathological correlation. Timely recognition and targeted management of RPN are essential to prevent potentially fatal complications.