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Non-steroidal anti-inflammatory drugs are not only potent analgesics and antipyretics but also nephrotoxins, and may cause electrolyte disarray. In addition to the commonly expected effects, including hyperkalemia, hyponatremia, acute renal injury, renal cortical necrosis, and volume retention, glomerular disease with or without nephrotic syndrome or nephritis can occur as well including after years of seemingly safe administration. Minimal change disease, secondary membranous glomerulonephritis, and acute interstitial nephritis are all reported glomerular lesions seen with non-steroidal anti-inflammatory use. We report a patient who used non-steroidal anti-inflammatory drugs for years without diabetes, chronic kidney disease, or proteinuria; he then developed severe nephrotic range proteinuria with 7 g of daily urinary protein excretion. Renal biopsy showed minimal change nephropathy, a likely secondary membranous glomerulonephritis, and acute interstitial nephritis present simultaneously in one biopsy. Cessation of non-steroidal anti-inflammatory drug use along with steroid treatment resulted in a moderate improvement in renal function, though residual impairment remained. Urine heavy metal screen returned with elevated levels of urine copper, but with normal ceruloplasmin level. Workup suggested that the elevated copper levels were due to cirrhosis from non-alcoholic fatty liver disease. The membranous glomerulonephritis is possibly linked to non-steroidal anti-inflammatory drug exposure, and possibly to heavy metal exposure, and is clinically and pathologically much less likely to be a primary membranous glomerulonephritis with negative serological markers.

Scleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots. The patient’s scleroderma renal crisis was severe, progressive, and refractory to the standard of care therapy: oral captopril. Biopsy showed a diffuse thrombotic microangiopathy and findings consistent with scleroderma renal crisis. We hypothesize that depletion of systemic vascular endothelial growth factor with intravitreal anti–vascular endothelial growth factor injections likely contributed to the particularly severe presentation seen in this case. Though the finding of a monoclonal gammopathy of undetermined significance is another complicating factor, this case suggests that vascular endothelial growth factor inhibition may be a newly recognized trigger of scleroderma renal crisis.

Certain diabetic and hypertensive patients started on intravitreal vascular endothelial growth factor inhibition for diabetic retinopathy may experience worsening of hypertension and proteinuria. The etiology of this is the newly recognized absorption of intravitreally injected vascular endothelial growth factor inhibitors, and the susceptibility of patients with pre-existing renal disease to exacerbations depends on the degree of systemic absorption. There are eighteen reported cases of worsening hypertension, woresening proteinuria, worsening renal function, thrombotic microangiopathy, and glomerular disease noted after initiation of intravitreal vascular endothelial growth factor blockade. This nineteenth case demonstrates worsening hypertension and proteinuria with the start of bevacizumab. Both blood pressure and proteinuria parameters showed overall improvement with switching to the less absorbed and lower potency agent ranibizumab. There was a slight rise in serum creatinine after bevacizumab therapy, which stabilized at a new baseline, and the serum creatinine remained stable on ranibizumab. There were no other nephrotoxic exposures that explained the mild rise in serum creatinine. Because of improvement in renal function and proteinuria, a renal biopsy was deferred for the time. This case re-demonstrates the risk of worsening proteinuria with vascular endothelial growth factor inhibitors when given intravitreally in some patients. The demonstration of improvement in blood pressure and proteinuria with the use of lower potency agents like ranibizumab is novel and an important concept confirming observations from pharmacokinetic studies. The switch to ranibizumab offers a therapeutic option when proteinuria worsens with intravitreal vascular endothelial growth factor blockade, and the patient requires ongoing intravitreal therapy for treatment of diabetic retinopathy.

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

Membranous glomerulonephritis is the most common glomerular disease in adults. Its primary form has been characterized with formation of phospholipase A2 receptor antibodies. Malignancy, infections, and autoimmune disorders are the most common causes of secondary membranous glomerulonephritis. We present a case of a 55-year-old African American female who presented with nephrotic range proteinuria and diagnosed with secondary membranous glomerulonephritis based on distinct pathological features on kidney biopsy and absence of serum phospholipase A2 receptor antibodies. She initially underwent extensive workup for malignancies, infections, and common autoimmune disorders which were all negative. Her proteinuria remained resistant to steroid treatment and she was treated with subcutaneous adrenocorticotropic hormone injections. Meanwhile, she was also diagnosed with the anti-muscle specific kinase antibody variant of myasthenia gravis. In literature, there are few case reports of myasthenia gravis as a cause of secondary membranous glomerulonephritis. In our case, the lack of other inciting factors also suggested this association.