A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

Genetic and biochemical features of the monogenic hereditary urolithiasis

Urolithiasis is a common urological problem. In most cases, this multifactorial pathology develops due to the combination of inherited low-penetrance gene variants and environment factors such as urinary tract infections and unbalanced diet. However, some cases are monogenic. These hereditary forms of urolithiasis manifest in childhood, and are characterized by multiple, bilateral and recurrent kidney stones and progress to chronic renal failure relatively early. Due to widening acceptance of exome and gene panel sequencing, substantially larger percentages of urolithiasis cases are now attributed to hereditary causes, up to 20% among patients of 18 years old or younger. Here we review genetic and biochemical mechanisms of urolithiasis, with an emphasis on its hereditary forms, including fermentopathies (primary hyperoxaluria, adenine phosphorobosyltransferase deficiency, phosphoribosyl-pyrophosphate-synthetase deficiency, xanthinuria, Lesch-Nihan syndrome) and these caused by membrane transport alterations (Dent's disease, familial hypomagnesia with hypercalciuria and nephrocalcinosis, hypophosphatemic urolithiasis, distal tubular acidosis, cystinuria, Bartter's syndrome). We suggest a comprehensive gene panel for NGS diagnostics of the hereditary urolithiasis. It is expected that accurate and timely diagnosis of hereditary forms of urolithiasis would enable the counselling of the carriers in affected families, and ensure personalized management of the patients with these conditions.

A Young Woman with Recurrent Kidney Stones: Questions on Hypokalaemic Tubular Acidosis

This paper discusses the diagnostic and therapeutic approach to the problem of a young woman presenting with recurrent kidney stones. In the clinical work-up, a hypokalaemic normal anion gap metabolic acidosis was found. The diagnostic tests to solve this common clinical problem and some therapeutic recommendations are discussed. Question on hypokalaemic tubular acidosis: 1. What is the significance of the plasma anion gap (PAG)? 2. How does one appreciate the respiratory component of the acid base status? 3. How does one perform tests for tubular acidification disturbances? 4. What is the pathogenesis of distal tubular acidification disturbances? 5. What is the explanation of the hypokalaemia in distal tubular acidosis? 6. What is the pathogenesis of nephrolithiasis in distal tubular acidosis? 7. How does one treat a patient with distal tubular acidosis and recurrent nephrolithiasis?

Management of the renal adverse effects of lithium

SummaryLithium is one of the most effective psychotropic drugs we have, but it is underused because of its low therapeutic index, the need for regular blood tests and perceptions about its adverse effects, including renal problems. The last include urinary concentration deficits and diabetes insipidus, chronic kidney disease (including renal failure), nephrotic syndrome, hypercalcaemia, hyperparathyroidism and distal tubular acidosis. This article reviews these adverse effects with special emphasis on their management.

Regulation of Luminal Acidification by the V-ATPase

Specialized cells in the body express high levels of V-ATPase in their plasma membrane and respond to hormonal and nonhormonal cues to regulate extracellular acidification. Mutations in or loss of some V-ATPase subunits cause several disorders, including renal distal tubular acidosis and male infertility. This review focuses on the regulation of V-ATPase-dependent luminal acidification in renal intercalated cells and epididymal clear cells, which are key players in these physiological processes.