Analysis of sex difference in the tubular reabsorption of lithium in rats

Lithium is used in the treatment of bipolar disorder. We previously demonstrated that two types of transporters mediate the tubular reabsorption of lithium in rats, and suggested that sodium-dependent phosphate transporters play a role in lithium reabsorption with high affinity. In the present study, we examined sex differences in lithium reabsorption in rats. When lithium chloride was infused at 60 µg/min, creatinine clearance and the renal clearance of lithium were lower, and the plasma concentration of lithium was higher in female rats. These values reflected the higher fractional reabsorption of lithium in female rats. In rats infused with lithium chloride at 6 µg/min, the pharmacokinetic parameters of lithium examined were all similar in both sexes. The fractional reabsorption of lithium was decreased by foscarnet, a representative inhibitor of sodium-dependent phosphate transporters, in male and female rats when lithium chloride was infused at the low rate. Among the candidate transporters mediating lithium reabsorption examined herein, the mRNA expression of only PiT2, a sodium-dependent phosphate transporter, exhibited sexual dimorphism. The present results demonstrated sex differences in the tubular reabsorption of lithium with low affinity in rats.

X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management

X-linked hypophosphatemic rickets (XLH) is the commonest inherited form of rickets. It is caused by an impaired regulation of fibroblast growth factor 23 (FGF23) due to a PHEX gene mutation, which leads to reduced tubular reabsorption of phosphate and renal 1α-hydroxylase activity and increased renal 24-hydroxylase activity. Hypophosphatemia associated with renal phosphate wasting, normal serum levels of calcium, parathyroid hormone, and 25-hydroxyvitamin D represents the main biochemical sign in affected patients. Patients with XLH show rickets and osteomalacia, severe deformities of the lower limbs, bone and muscular pain, stunted growth, and reduced quality of life. However, XLH is a multisystemic disorder requiring multidisciplinary approaches in specialized subdisciplines. Severe complications may occur in patients with XLH including craniosynostosis, hearing loss, progressive bone deformities, dental and periodontal recurrent lesions, and psychosocial distress. Moreover, long-term conventional treatment with active vitamin D metabolites and oral inorganic phosphate salts may cause endocrinological complications such as secondary or tertiary hyperparathyroidism, and adverse events in kidney as hypercalciuria, nephrocalcinosis, and nephrolithiasis. However, conventional treatment does not improve phosphate metabolism and it shows poor and slow effects in improving rickets lesions and linear growth. Recently, some trials of treatment with recombinant human IgG1 monoclonal antibody that targets FGF23 (burosumab) showed significant improvement of serum phosphate concentration and renal tubular reabsorption of phosphate that were associated with a rapid healing of radiologic signs of rickets, reduced muscular and osteoarticular pain, and improved physical function, being more effective for the treatment of patients with XLH in comparison with conventional therapy. Therefore, a global management of patients with XLH is strongly recommended and patients should be seen regularly by a multidisciplinary team of experts.

Imerslund-Grasbeck syndrome- a rare cause of megaloblastic anemia in an infant with homozygous mutation in CUBN gene: a case report and review of the literature

Megaloblastic anaemia is one of the important causes of pancytopenia in children and nutritional deficiencies of vitamin B12 and folate are the most common causes comprising 95% of these cases. Defects in absorption, transport and metabolism of vitamin B12 are well described, however, are very rare. We report a rare case of Imersland Grasbeck syndrome, in an infant who presented with pancytopenia, with defective absorption of B12-intrinsic factor complex at the ileum and defective tubular reabsorption of proteins in renal tubule due to same protein defect caused by mutations in two genes – CUBN (cubilin) and AMN (amnionless).

Tubulopathy meets Sherlock Holmes: biochemical fingerprinting of disorders of altered kidney tubular salt handling

Evolution moves in mysterious ways. Excretion of waste products by glomerular filtration made perfect sense when life evolved in the ocean. Yet, the associated loss of water and solutes became a problem when life moved onto land: a serious design change was needed and this occurred in the form of ever more powerful tubules that attached to the glomerulus. By reabsorbing typically more than 99% of the glomerular filtrate, the tubules not only minimise urinary losses, but, crucially, also maintain homeostasis: tubular reabsorption and secretion are adjusted so as to maintain an overall balance, in which urine volume and composition matches intake and environmental stressors. A whole orchestra of highly specialised tubular transport proteins is involved in this process and dysfunction of one or more of these results in the so-called kidney tubulopathies, characterised by specific patterns of clinical and biochemical abnormalities. In turn, recognition of these patterns helps establish a specific diagnosis and pinpoints the defective transport pathway. In this review, we will discuss these clinical and biochemical “fingerprints” of tubular disorders of salt-handling and how sodium handling affects volume homeostasis but also handling of other solutes.

Effect of Experimental Fanconi Syndrome on Tubular Reabsorption of Lithium in Rats

Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Using samples of plasma and bladder urine during the mannitol infusion, renal parameters were determined. Pharmacokinetic parameters of lithium were obtained using samples during the lithium chloride infusion. Maleic acid decreased creatinine clearance and increased the fractional excretion of glucose and phosphate, suggesting the induction of Fanconi syndrome. In rats with Fanconi syndrome, plasma concentration of lithium was increased, and its renal clearance was decreased. No effect on the fractional excretion of lithium was exhibited. This study represents that the tubular reabsorption of lithium was impaired to the same degree with glomerular filtration in rats with experimental Fanconi syndrome and that the dysfunction of the tubular reabsorption of glucose and phosphate was more severe. It is possible that Fanconi syndrome inhibited the reabsorption of lithium at the proximal tubule and facilitated the reabsorption of lithium from the loop of Henle to the collecting duct.

SGLT2 Inhibitors: A Noval Therapuetic Agent in the Treatment of Diabetic Kidney Disease

Sodium Glucose Co-transporter2 inhibitors are one of the latest anti diabetic drugs that are approved by USFDA. It include Dapagliflozin, Canagliflozin , Ipragliflozin,Empagliflozin, Tofogliflozin,and Luscogliflozin. They act by inhibiting tubular reabsorption of glucose in kidney and increasing urinary excretion of glucose. SGLT2 inhibitors reduce the workload of the proximal tubules and improve tubulointerstitial hypoxia, and allow fibroblasts to start normal erythropoietin production, and thereby exhibit renoprotection .These drugs have beneficial role in the reduction of HbA1c, cardiovascular risk factors and proteinuria. Use of SGLT2 inhibitor is contraindicated in patients with estimated GFR less than 30 mL/min or End stage renal failure Genitourinary infections are most common adverse effects associated with these drugs, predominantly in female. Keywords: Diabetes Mellitus, Diabetic Nephropathy, Hyperfiltration, Natriuresis, Macroalbuminuria, Endothelial dysfunction, Intraglomerular filtration, ketoacidosis, amputations, apoptosis

C3 Glomerulonephritis Along With Light Chain Tubular Reabsorption in Multiple Myeloma: A Case Report

Background: Multiple myeloma has different kinds of renal injuries. C3 glomerulonephritis (C3GN) is characterized by abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of complement system. The association between C3GN and multiple myeloma had been well established. However, the mild renal injury of C3GN in the multiple myeloma patients with high level of light chain had not been reported.Case presentation: A 55 years old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy and renal biopsy, this patient was diagnosed with IgA type multiple myeloma accompanied by C3GN and light chain tubular reabsorption. Although he had a higher level of lamda serum free light chain, the renal injury of this patient was mild. After treated with 4 courses of BD, one course of PAD and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function. Conclusions: In multiple myeloma, the condition for light chain to result in renal impairment of C3GN is that the light chain reaches a certain level and lasts for a long time. Early diagnosis and early intensive treatment are extremely important for the prognosis of such patients.

Search for new diagnostic markers of renal function in pregnant women

Over the past few years, the prevalence of chronic kidney disease in pregnant women has been increasing rapidly, which is one of the most important problems of obstetrics, urology, and nephrology. The severity of the disease is assessed by a decrease in glomerular filtration rate (GFR). However, modern formulas of GFR give errors, therefore, it is necessary to search for new diagnostic markers of renal function in pregnant women. It is believed that elimination of cystatin C from the circulation by more than 99% is carried out by the kidneys. In an intact form, this molecule is not thought to undergo either tubular reabsorption or secretion. In this sense, cystatin C can be considered an almost ideal marker of GFR. This article discusses the possibilities of using cystatin C as a marker of renal function in pregnant women.