Overview

Renal papillary necrosis (RPN) is a term that refers to the death of cells (coagulative necrosis) in the renal medullary pyramids and papillae, which are cone-shaped structures found within the kidney’s inner tissue (medulla). This is caused by a cascade of factors that leads to ischaemia, a lack of blood flow to a part of your body. 

Ischaemic necrosis is the death of cells due to the lack of blood flow and hence oxygen. It is quite common in the renal medulla and its papillae because of the compromised supply of blood and the high osmolarity (less water compared to the molecules within a fluid, e.g. blood, urine) of the environment. 

The clinical picture of RPN depends on the degree of blood flow cutoff, the presence of aggravating factors, the condition of the patient, and the number of affected papillae. This can occur as a complication when there is irreparable damage to the patient, as the papillae become necrotic.^1,2

Anatomy of renal papillae

The renal pyramid contains renal papillae located on the tip or pointed extremities. A calyx minor, located in the centre of the renal pelvis, receives each papilla.

The papillae have a unique characteristic that can be defined as a sieve, resulting from several small holes in their outer layer. Each of these holes is a small duct known as the papillary duct, which collects urine that traverses from the collecting ducts of the renal pyramid.

The renal papillae act as channels for renal filtration by allowing urine to pass through the minor calyces of the renal pelvis from the papillary ducts.³

Causes

Renal papillary necrosis (RPN) is a complex condition with various causes that may co-occur in the following settings: kidney infection (pyelonephritis), blockage of the urogenital passage, drug abuse of non-steroidal anti-inflammatory drugs (NSAIDs), type 2 diabetes mellitus (DM), and the COVID pandemic.⁴

Important considerations regarding NSAIDs and renal papillary necrosis (RPN) 

• They relieve pain, fever and prevent inflammation. However, they are toxic to the kidney
• Chronic use, especially of aspirin, can cause analgesic nephropathy and renal papillary necrosis

Action of NSAIDs

• Generally, they do not increase blood pressure or cause renal impairment in healthy patients
• However, in patients with renal ailments, as noted, NSAIDs inhibit renal prostaglandin synthesis, which results in a reduction of renal blood flow, disruption of filtration and osmolarity balance

How is RPN induced by NSAIDs?

• Toxic to medullary cells
  • Destroys prostaglandin-producing cells, which play an important role in regulating salt and water balance within the kidneys. It reduces water reabsorption, hence leading to difficulties in making the urine more concentrated
  • This causes swelling of cells, vessel leaking, calcification, and the loss of renal papillae
• Ischaemic lethal injury
  • This is because NSAIDs cause the inhibition of cyclooxygenase, which lowers the levels of prostaglandins and causes renal ischaemia due to low renal blood flow
• NSAIDS Influence on angiotensin converting enzymes (ACE) inhibitors and diuretics
  • ACE inhibitors lower blood pressure, and NSAIDs reduce the effectiveness of these types of medication, which can lead to severe kidney problems
  • Diuretics deplete blood volume in the body, enhancing the risk of acute tubular necrosis and RPN

Risk factors of RPN

RPN is more likely to occur in aged patients, people assigned female at birth (AFAB) with prior renal illnesses, high blood pressure, diabetes, nephritic syndrome, congestive heart failure, reduced fluid levels, or liver scarring.⁴

Diagnosis of papillary necrosis

The basic diagnostic evaluation consists of a urinalysis (both routine and microscopic), a full blood count, a metabolic panel, and testing for prothrombin time and activated partial thromboplastin time, which tests how long it takes for blood to clot. When a patient is unconscious, it is necessary to place an arterial blood gas probe and conduct standard electrocardiography and radiography of the chest. In cases where there is a concern about a severe blockage, a CT of the abdomen and pelvis or renal ultrasound will be performed, and a urology consultation will be requested immediately.⁵

Finally, patients presenting with haematuria (blood in the urine) but without any signs of infection in the urine sample and without inflammatory changes in the pelvis call for a complete evaluation. This includes cystoscopy and upper tract imaging for disorders such as renal/ureteral/bladder stones, renal tumours, renal pelvis/ureter tumours, and bladder tumours. 

Routine and microscopic urinalysis and urine culture should also be carried out using appropriate specimen collection techniques (ie, sterile catheterisation or clean-catch midstream). While consideration may be given to urine cytology, it is seldom required and needs to be more conclusive.

The typical results of urinalysis performed on patients demonstrating acute kidney failure include the presence of protein, cellular elements, bacteria, and excessive dilution of the urine. More than half of the patients studied had raised white blood cell count (leucocytosis) and raised nitrogenous products (azotemia) in the blood. These outcomes may result in obstruction, a toxic, metabolic, or inflammatory injury. 

Patients with known or probable obstruction require the urgent attention of a urologist.

If the clinical picture is suggestive, one or more of the following causes of renal papillary necrosis are investigated: 

• Pyelonephritis
• Obstruction of the urinary tract
• Sickle cell disease
• Tuberculosis
• Cirrhosis
• Over-the-counter analgesics 
• Transplant rejections
• Polydipsia

In addition to clinical findings, investigations such as the following may also be carried out: 

• Complete blood count
• Tuberculin test
• Assessment of liver function
• Measurement of plasma ammonia levels
• Plasma and urinary acetylsalicylic acid and paracetamol concentration
• Glycosylated haemoglobin
• Levels of cyclosporine or tacrolimus 

Long-term monitoring

Appropriate follow-up care entails seeing a physician to avoid future complications or treat any comorbid conditions. Follow-up care may include a multi-speciality referral if your primary care physician determines it as appropriate.

A cessation of painkiller use and attention to blood pressure management ensure good renal function. Preventative treatment of asymptomatic urinary infections with long-term low-dose antibiotics lowers morbidity from renal papillary necrosis. If a regular painkiller is necessary, it is advised that you drink plenty of water. Studies have shown that lesions (injury) in long-term painkiller users may not develop if there is adequate hydration.

In people with obstructive uropathy who have no plan for surgery, the use of preventative antibiotics would be of significant benefit. Those undergoing any procedures on the urinary tract need to be seen by a urologist for a post-procedure follow-up, especially if any further intervention is necessary. In patients with haematuria, a full workup by the urologist is warranted.¹

Complications

Any area of necrotic papillae may serve as a welcoming site for both infectious agents and lithogenic material (forming kidney stones). Such necrotic deposition is capable of causing severe pyelonephritis (kidney infection), perirenal abscess formation, and even septicaemia (severe bloodstream infection).⁸ The formation of stones can further complicate the necrosis since the bacteria are protected within the stones. Along with this, stones can also grow, leading to further obstruction, hypertension (high blood pressure), and increasing ischaemia.^6,7

In cases of flank pain and haematuria, especially where no stones are evident and particularly among people with diabetes, RPN should always be kept in mind as a differential cause of ureteric obstruction.¹

Prevention

To conclude, while the offered approach seems reasonable as a measure of prevention, preventative antibiotics are not standard treatment among individuals with renal papillary necrosis. The benefits of antibiotics need to be investigated further, and the prevention of hospital-acquired urinary tract infections should be prioritised. In cases where urinary catheters are required, or when a patient has urinary stasis (difficulty in passing urine) or complete blockage, risk factors, antibiotics given as a precaution may help.⁷

Summary

Renal papillary necrosis is a complication stemming from ischaemia that occurs during complete blockage of blood flow to the kidneys (renal vascular occlusion). Papillary necrosis may also produce urinary outflow obstruction due to necrotic papillae that shed, leading to decreased or no urine output. Pain and haematuria are the common clinical symptoms. A CT urogram will reveal a small area of contrast centred at the papillary regions with shed necrotic material appearing as filling defects.

Assessing kidney health in renal papillary necrosis (RPN) consists of periodic laboratory tests for renal function, evaluation of blood pressure, and imaging. Sufficient hydration and preventive antibiotics can help in avoiding further injury, especially in long-term users of painkillers or those with obstructive uropathy. Follow-up care from a urologist is important for these patients, especially those with haematuria or those about to have urinary procedures.