Pembrolizumab-induced Acute Tubulointerstitial Nephritis Accompanying Fanconi Syndrome and Type 1 Renal Tubular Acidosis.

Pembrolizumab, an immune checkpoint inhibitor, is used to treat a variety of refractory malignancies. However, these agents are sometimes associated with immune-related adverse events. A 71-year-old woman received pembrolizumab-integrated chemotherapy to treat her recurrent mandibular gingival cancer. Five months after stopping pembrolizumab, she developed acute tubulointerstitial nephritis associated with Fanconi syndrome and type 1 renal tubular acidosis, which resolved with steroid therapy. We experienced a case of pembrolizumab-induced Fanconi syndrome and type 1 renal acidosis. We recommend follow-up of the tubular function in addition to the renal function even after discontinuation of pembrolizumab.

Hypophosphataemic osteomalacia due to cadmium exposure in the silver industry.

Chronic heavy metal exposure and the health hazards that ensue are important public-health problems. We highlight the occurrence of hypophosphataemic osteomalacia due to chronic cadmium exposure in the silver industry in India. Three silversmiths presented similarly with clinical, biochemical and radiological evidence of hypophosphataemic osteomalacia. Considering their occupation, their blood samples were screened for heavy metals and were found to have toxic levels of cadmium. They were initiated on neutral phosphate and calcitriol. On follow-up, they reported significant reduction in severity of symptoms. It is essential to maintain a high index of suspicion in diagnosing this condition. A thorough knowledge of the occupational background of patients, as well as ambient conditions at the workplace is of utmost importance in contemplating the possibility of such rare occurrences. Moreover, regulatory agencies and policy makers ought to survey the silver industry and ensure that the metals used are within permissible safe limits of exposure.

Gut It Out: Laxative Abuse Mimicking Distal Renal Tubular Acidosis.

BACKGROUND: Distal renal tubular acidosis (dRTA) can be inherited or acquired. CASE PRESENTATION: Here, we describe the case of a 45-year-old female patient with non-anion gap metabolic acidosis, hypokalemia, and alkaline urine. She had a history of rheumatoid arthritis and kidney stones and failed to acidify urine upon the fludrocortisone and furosemide test. Therefore, the diagnosis of dRTA secondary to an autoimmune disease was made. A kidney biopsy was examined for markers of acid-secretory intercalated cells. Surprisingly, no obvious difference in the relative number of acid-secretory intercalated cells or in the distribution of major proteins involved in acid secretion was found. Furthermore, increasing doses of potassium citrate failed to correct the hypokalemia and acidosis. Since these findings were rather atypical for autoimmune dRTA, alternative causes of her hypokalemia and metabolic acidosis were sought. The patient was found to chronically consume laxatives, which can also cause kidney stones and may result in a false-positive urinary acidification test. CONCLUSION: Chronic laxative abuse may mimic dRTA and should therefore be considered in unexplained hypokalemia with non-anion gap metabolic acidosis.

Tenofovir and Severe Symptomatic Hypophosphatemia.

Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi's syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.

Proximal Renal Tubular Acidosis (Fanconi Syndrome) Induced by Apremilast: A Case Report.

Apremilast is a recently developed phosphodiesterase 4-inhibitory medication approved for use to treat psoriasis and psoriatic arthritis. We report a case of Fanconi syndrome and proximal renal tubular acidosis that was associated with this medication. Our patient was started on treatment with apremilast 2 weeks before his admission. On arrival, laboratory test results were significant for hypokalemia, hyperchloremic metabolic acidosis, low uric acid concentration, positive urine anion gap, and proteinuria, which resolved on discontinuation of the drug. Two months after the hospitalization, he was restarted on apremilast therapy; 17 days after resumption, the patient was admitted for similar laboratory values, which again improved when apremilast treatment was discontinued. After discharge, laboratory values remained normal without long-term electrolyte repletion. Proximal renal tubular acidosis (Fanconi syndrome) with quick correction of electrolyte concentrations on discontinuation of the drug was diagnosed. Our patient lacked evidence of other causes. Our patient fulfilled criteria associated with this disease and responded well off treatment with the offending agent. Literature review did not reveal prior cases associated with this medication.

Transfusion-dependent thalassaemic patients with renal Fanconi syndrome due to deferasirox use.

AIM: Deferasirox is a new oral iron chelating agent with several cases reporting renal adverse events in recent years. Our aim was to identify the incidence of deferasirox-related Fanconi syndrome (FS) and its risk factors. METHODS: All transfusion-dependent thalassaemic patients who received deferasirox at the outpatient department of the National Taiwan University Hospital (NTUH) from January 2006 to February 2014 were evaluated. RESULTS: This cohort study included 57 patients, and mean age of deferasirox initiation was 18.2 ± 7.7 years. After 6.9 ± 1.8 years of follow-up, 5 in 57 (8.8%) thalassaemic patients had FS. Age of starting deferasirox negatively correlated with incidence of FS (correlation coefficient -0.892, P = 0.008). Other factors were not significantly associated with FS. Serum creatinine level at the start of deferasirox compared to at the end of study or onset of FS did not show significant change (P = 0.277). All the deferasirox-related FS manifested with proximal renal tubular acidosis and hypophosphataemia, which needed specific treatment or withdrawal of deferasirox use. CONCLUSIONS: We recommend that children, especially of young age, who regularly use deferasirox should undergo routine urinalysis and blood testing for early detection of FS.

Hyperchloraemic metabolic acidosis induced by the iron chelator deferasirox: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Deferasirox is a new treatment of iron overload that is administered orally once-a-day, resulting in better acceptance in patients. Deferasirox-induced renal tubular dysfunction has been reported on very rare occasions. CASE SUMMARY: A 17-year-old adolescent with ß-thalassaemia on deferasirox 30 mg/kg daily presented with isolated hyperchloraemic metabolic acidosis (bicarbonate 12·9 mM, sodium 137 mM, chloride 111 mM, potassium 3·6 mM). Acidosis resolved after withdrawing deferasirox. Naranjo adverse drug reaction scale suggested that the likelihood that deferasirox was responsible for acidosis was probable. Eight cases of metabolic acidosis have been reported in patients treated with deferasirox. In most cases, acidosis was associated with further features of renal tubular dysfunction. WHAT IS NEW AND CONCLUSION: We describe herein a case of metabolic acidosis in the setting of treatment with the deferasirox. Our case and the literature indicate a potential risk of kidney toxicity on this agent.

Distal renal tubular acidosis that became exacerbated by proton pump inhibitor use.

Acid-base imbalances and electrolyte disorders induced by proton pump inhibitors (PPIs) are extremely rare. However, under certain conditions, PPIs may cause metabolic acidosis or hypokalemia, probably due to an inhibitory action on the proton pump that contributes to H(+) and K(+) homeostasis in the kidney. We herein present a case of marked hypokalemia accompanied by distal renal tubular acidosis in which a PPI appeared to contribute to the pathophysiology of metabolic acidosis.

Renal tubular acidosis secondary to capecitabine, oxaliplatin, and cetuximab treatment in a patient with metastatic colon carcinoma: a case report and review of the literature.

We report a case of renal tubular acidosis (RTA) secondary to capecitabine, oxaliplatin, and cetuximab administration in a 63-year-old woman with liver metastasis from colon carcinoma who had partial treatment response. On day 5 posttreatment, she arrived to the emergency room with severe weakness, and blood tests demonstrated hypokalemia with metabolic acidosis. Urine potassium levels were elevated, and the transtubular potassium gradient (TTKG) was 6.6, consistent with hypokalemic RTA with associated Fanconi syndrome, which presented as hyperphosphaturia, uricaciduria, and loss of protein and sugar in the urine. She was treated with intravenously administered potassium and fluids. RTA is one type of nephrotoxicity induced by chemotherapy, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by chemotherapy in cancer patients has not yet been clearly elucidated. Oncologists should therefore be aware of the potential for RTA to occur after capecitabine, oxaliplatin, and cetuximab treatment, especially in the context of other predisposing factors.

Familial tumoral calcinosis caused by a novel FGF23 mutation: response to induction of tubular renal acidosis with acetazolamide and the non-calcium phosphate binder sevelamer.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is an uncommon disease characterized by periarticular calcifications produced by the deposition of amorphous extraosseous calcifications of hydroxyapatite. It is associated with hyperphosphatemia due to increased tubular phosphate reabsorption, despite normal renal function and normal plasma PTH levels. The disease can be caused by inactivating mutations in either the fibroblast growth factor 23 (FGF23) gene, the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene or in human KLOTHO (KL) gene. Herein, we describe a Caucasian 3-year-old girl with tumoral calcinosis who presented with elevated serum phosphorus levels and a large calcified mass at her left elbow which led to ulceration of the skin. Treatment with the phosphate binder sevelamer and the carbonic anhydrase inhibitor acetazolamide successfully reduced the serum phosphate levels and led to a reduction of the calcified mass. This medical management has not been described previously. Her 7-month-old sister also had elevated serum phosphate levels, but did not have ectopic calcifications. Sequencing analysis revealed a novel homozygous FGF23 missense mutation (c.367G>T, p.Gly123Trp) in both siblings while the parents were carriers of the mutation.

Combined renal tubular acidosis and diabetes insipidus in hematological disease.

BACKGROUND: A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure. INVESTIGATIONS: Physical examination, blood and urine analyses, kidney biopsy and tonicity balance. DIAGNOSIS: Fanconi syndrome with proximal (type II) renal tubular acidosis caused by myeloma kidney. Renal tubular acidosis was complicated by probable nephrogenic diabetes insipidus and acute renal failure. MANAGEMENT: Potassium supplementation, sodium bicarbonate therapy, intravenous fluid therapy and dialysis.

Pemetrexed-induced acute renal failure, nephrogenic diabetes insipidus, and renal tubular acidosis in a patient with non-small cell lung cancer.

We report a patient with metastatic non-small cell lung cancer who developed renal toxicities manifest as acute renal failure associated with nephrogenic diabetes insipidus and distal renal tubular acidosis following sequential therapy with pemetrexed. The nephrotoxicity occurred concomitantly with severe myelosuppression. We postulate renal tubular toxicity may account for distinct patterns of injury including acute renal failure and tubular cell dysfunction of the distal nephron.

Topiramate and severe metabolic acidosis: case report

Topiramato pode produzir raramente uma acidose metabólica através da inibição da anidrase carbônica no túbulo distal do néfron - acidose tubular renal do tipo 2. Relatamos o caso de mulher de 40 anos previamente saudável que desenvolveu quadro de acidose metabólica assintomática grave, sem outra etiologia identificável, durante uso de topiramato na dose de 100mg/dia por três meses. Este efeito colateral, embora infrequente, parece ser imprevisível e requer atenção cuidadosa.

Antiviral drug-induced nephrotoxicity.

Drug-induced kidney injury is a major side effect in clinical practice, frequently leading to acute renal failure (ARF). It accounts for more than 2% to 15% of cases of ARF in patients admitted to the hospital or in the intensive care unit, respectively. The exact frequency of nephrotoxicity induced by antiviral drugs is difficult to determine. Antiviral drugs cause renal failure through a variety of mechanisms. Direct renal tubular toxicity has been described with a number of new medications with unique effects on epithelial cells of the kidney. These include cidofovir, adefovir dipivoxil, and tenofovir, as well as acyclovir. Additionally, crystal deposition in the kidney may promote the development of renal failure. Several different drugs have been described to induce crystal nephropathy, including acyclovir and the protease inhibitor indinavir. Renal injury associated with antiviral drugs involves diverse processes having effects on the renal transporters, as well as on tubule cells. In this article, we review the pathogenesis of antiviral drug-induced kidney injury, common nephrotoxic renal syndromes, and strategies for preventing kidney injury.

Possible association between cell membrane band 3 impairment function and renal tubular acidosis (liver diseases, malignancies and adverse drug reactions).

Renal tubular acidosis (RTA) more frequently develops in case of chronic diseases of inflammatory-immunological origin. RTA is well known to be associated with chronic liver disease (CLD), with nephrolithiasis, common cases of RTA occur among cancer patients. Abnormalities in the expression or function of band 3 in cell membrane may play a role in the pathogenesis of RTA. Cl-/HCO3- anion exchanger (AE2) is an isoform of band 3 protein, which is expressed in cell membranes of organs such as liver cells and kidney endothelium. There are reports on downregulated AE2 immunoreactivity in the liver of patients with chronic liver diseases and in the kidney tubular tissue of patients with RTA. The proteolytic damage of cell membrane band 3 in tissues could be related to inflammatory-immunological processes. Another important factor able to disturb the band 3 function is medicinal products used in the treatment of certain pathologies. The active substance of a drug itself may have a direct effect on this protein or trigger a pathological process. In such cases ADR can take place and may be evaluated as such. Acid-base disturbances, notably metabolic acidosis, are a serious complication of drug treatment. Reduced AE2 expression or its changed activity (congenital or acquired) could be related with alterations of intracellular pH. This could lead to antigenic changes and autoimmunity. The derangement of band 3 function in organ cell membrane could act as a factor which creates an "acidotic environment" for organ cells. Such circumstances could be the reason for unsuccessful treatment or determine resistance of tumor treatment. The understanding of the mechanisms of RTA development, early diagnostics, and knowledge of the drugs that can cause RTA, are of particular practical significance.

Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report.

FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.