Renal Papillary Necrosis (RPN) in an African Population: Disease Patterns, Relevant Pathways, and Management

Abstract

Renal papillary necrosis (RPN) is characterized by coagulative necrosis of the renal medullary pyramids and papillae. Multiple conditions and toxins are associated with RPN. Several RPN risk factors, or POSTCARDS, have been identified, with most patients presenting with RPN having at least two contributing risk factors. Currently, there is no specific test to diagnose and confirm RPN; however, several imaging tools can be used to diagnose the condition. RPN is currently underdiagnosed in African populations, often with fatal outcomes. In African clinical settings, there is a lack of consensus on how to define and describe RPN in terms of kidney anatomy, pathology, endourology, epidemiology, the identification of African-specific risk factors, the contribution of oxidative stress, and lastly an algorithm for managing the condition. Several risk factors are unique to African populations including population-specific genetic factors, iatrogenic factors, viral infections, antimicrobial therapy, schistosomiasis, substance abuse, and hypertension (GIVASSH). Oxidative stress is central to both GIVASSH and POSTCARDS-associated risk factors. In this review, we present information specific to African populations that can be used to establish an updated consensual definition and practical grading system for radiologists, urologists, nephrologists, nuclear physicians, and pathologists in African clinical settings.

Keywords: HIV; coagulative necrosis; diabetes; genetic; oxidative stress; renal papillary necrosis; schistosomiasis free radicals.

Figure 1

An illustration of renal papilla and fornix. (A) Depicts the position and structure of the renal papilla which lies within the renal medulla; and (B) the blood supply to the renal papilla showing that as the arteries narrow toward the papilla, the blood flow reduces predisposing the papilla to ischemia which could lead to necrosis.

Figure 2

Features of renal papillary necrosis (RPN) in a 50-year-old female. (A) The computed tomography (CT) scan indicates spongiform lesion in a lower pole and posterior midpole regions. There are multiple small locules consistent with tubulo-interstitial nephritis or RPN. The patient was diagnosed with human immunodeficiency virus (HIV), pulmonary tuberculosis (TB) and immune reconstitution inflammatory response syndrome (IRIS); (B) the whitish cotton wool type lesion seen with flexible ureteroscopy in the lower pole of the left kidney.

Figure 3

Features of RPN in Fraley syndrome. This is a histologically confirmed case of RPN after partial nephrectomy. The CT scan denotes the upper pole obstruction with hydrocalycosis as depicted by the arrow. The per-operative findings image post excision are also shown.

Figure 4

Gross anatomy and histological images showing. (A) Kidney with RPN that appears largely fibrotic with marked chronic interstitial nephritis; (B) inflammatory features are shown in the drawn region as a feature of neutrophil infiltration. In places, aggregates of mononuclear lymphocytes form mature lymphoid follicles. Plasma cells are also present; (C) an image of a kidney with RPN. The indicated white regions are due to lack of blood supply which cause tissue necrosis; (D) an image depicting coagulative necrosis. Ghost cells are denoted by the number 1, 2 depicts foamy macrophages and 3 is neutrophil debris.

Figure 5

Emerging diagnostic paradigm shift for RPN diagnosis. Several approaches could be considered when investigating RPN. (1) Ultrasound is used for differential diagnosis which could detect advanced RPN or other diseases such as ureteric stone; (2) CT scan is more sensitive and mostly specific in detecting kidney diseases but early stages of RPN can still be missed at this point; (3) endourological approach could be more determinant during an emergency (hematuria) or elective procedure; (4) additionally, other diagnostic assays could be investigated as reliable methods that could assist in detecting and diagnosing the RPN early and allow sufficient time to prevent further damage to the kidney.

Figure 6

Additional suggested mnemonic RPN risk factors. Histologically, RPN is characterized by several features with the main initiator being coagulative necrosis of the renal papilla and the medullary pyramids. These features are still a valuable diagnostic representation of RPN as listed in POSTCARDS. However, several African patients present with additional features that should be considered to allow clinicians to tackle the disease more effectively.

Figure 7

Oxidative stress in acute and chronic kidney disorders is associated with the development of RPN and fibrosis. A high concentration of oxidative stress products is associated with several toxic factors, subsequently triggering an inflammatory response, and leading to kidney damage.

Figure 8

Major sources of reactive oxygen species (ROS) in the kidney.

Figure 9

ROS associated with renal fibrosis. Renal fibrosis is mainly associated with inflammation however, it is now widely accepted that ROS also contributes significantly to renal fibrosis. Ischemia/reperfusion is associated with the production of ROS. Ischemia/reperfusion is also one of the major factors associated with the induction of RPN. During fibrosis, renal tubulointerstitial fibrosis, renal parenchyma collapses due to the accumulation of collagen fibers and inflammatory markers. The glomerulus can be scarred and collapse leading to proteinuria. Excessive ROS production can lead to mitochondrial dysfunction which exacerbates injury of kidney tubules. ROS-reactive oxygen species.

Figure 10

Summary figure depicting RPN proposed algorithm management. Besides identifying risk factors and the role of oxidative stress associated with RPN, it is essential that a multidisciplinary approach is considered for early detection of the disease. Integrated management will ensure successful disease outcomes. TAC: total antioxidant capacity; T99GH: technetium 99 glucoheptonate.