Acute kidney injury (AKI), a sudden reduction in kidney function, is seen in some people with covid-19 infection. A subset of patients develop severe AKI and require renal replacement therapy (RRT). As in many settings, the development of AKI is associated with an increased risk of mortality.1 2 Although our understanding is incomplete, a picture is emerging from case reports and autopsy series of covid-19 specific causes of AKI. Intrinsic renal pathology including thrombotic vascular processes, viral mediated tubular cell injury, and glomerulonephritis have been reported, as well as AKI resulting from extrinsic factors such as fluid depletion, multi-organ failure, and rhabdomyolysis.3-7 Anecdotal reports have emerged of proximal tubular injury with Fanconi syndrome that manifests as hypokalaemia, hypophosphataemia, normal anion gap metabolic acidosis, and hypovolaemia from salt wasting. Importantly, AKI can occur at all stages of covid-19 infection, so clinical vigilance and consideration of risk factors for AKI alongside early detection and diagnosis are essential components of general supportive care. Fluid management is central to this. This article summarises key points from the National Institute for Health and Care Excellence (NICE) covid-19 rapid guideline on AKI in hospital.

Background Primary Sjögren syndrome (pSS) is a common autoimmune condition which primarily affects epithelial tissue, often including the kidney causing either tubulointerstitial nephritis (TIN) or more rarely, an immune complex related glomerulonephritis. Methods We describe the clinical, biochemical and histological characteristics of 12 patients with pSS related TIN and their response to treatment with antiproliferative agents. All 12 patients were investigated and treated at the UCL Centre for Nephrology in London. Results All patients had TIN demonstrated via needle biopsy; immunophenotyping showed that the interstitial infiltrate was predominantly a CD4+ T-cell infiltrate. Urinary acidification testing demonstrated distal renal tubular acidosis in 8 patients. Proximal tubular dysfunction was present in 5 patients. All but 1 patient were treated with antiproliferative agents and most also with a reducing course of steroids. In the treated patients, there was a significant improvement in the serum creatinine and measured GFR. Conclusion Patients with pSS TIN have significant renal impairment and other functional tubular defects. There is a mononuclear lymphocytic infiltrate on renal biopsy and this appears to be mainly a CD4+ T-cell infiltrate. Treatment with mycophenolate (and corticosteroids) improves the renal function in patients with pSS TIN.

BACKGROUND/AIMS:Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. METHODS:We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. RESULTS:All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. CONCLUSIONS:This autosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis.

A 33-year-old woman of African origin received a live related donor allograft. She had end-stage renal disease secondary to lupus nephritis and was undergoing hemodialysis and had a background of sickle cell disease. She underwent uncomplicated transplant surgery with immediate graft function and a baseline creatinine level of 0.79 mg/100 ml. Four months after transplantation she presented with a rise in serum creatinine to 1.92 mg/100 ml. Duplex ultrasound showed a patent renal artery and vein and no features of obstruction. There was reduced vascularity within the renal cortex, and shunting of capsular vessels into the peripheral renal cortex, with loss of corticomedullary differentiation. Tc-99m MAG-3 renal scan (Figure 1) was performed, followed by renal biopsy (Figure 2).Figure 2Cortical renal transplant biopsy stained with hematoxylin and eosin (original magnification × 40).View Large Image Figure ViewerDownload (PPT) What is the cause of this abnormal MAG-3 renogram? Tc-99m MAG-3 renogram showed patchy impairment of perfusion, which contrasted dramatically with the uniform uptake noted on the renogram performed early in the postoperative period (Figure 1). Percutaneous renal biopsy showed focal cortical necrosis and acute tubular damage consistent with ischemia. Some glomeruli contained clumped, probably sickled red cells (Figure 2). There were no features of rejection. Magnetic resonance angiography demonstrated wedge-shaped areas of infarction in segmental artery territories with normal major vessels (Figure 3). Allograft function has remained stable but significantly impaired. Chatterjee et al. described a similar case in a male patient with known sickle cell trait (hemoglobin AS). Following what appeared clinically to be an episode of acute rejection resulting in graft loss, histological examination demonstrated extensive intravascular erythrocyte sickling.1.Chatterjee S.N. Lundberg G.D. Berne T.V. Sickle cell trait: possible contributory cause of renal allograft failure.Urology. 1978; 11: 266-268Abstract Full Text PDF PubMed Scopus (10) Google Scholar In one series of patients with sickle cell disease or trait undergoing renal transplantation there was a high incidence of crises in the first year, with a worse-than-expected 1-year graft survival at 67%.2.Chatterjee S.N. National study on natural history of renal allografts in sickle cell disease or trait.Nephron. 1980; 25: 199-201Crossref PubMed Scopus (39) Google Scholar A further study has shown comparable short-term outcomes, but reduced long-term graft survival.3.Ojo A.O. Govaerts T.C. Schmouder R.L. et al.Renal transplantation in end-stage sickle cell nephropathy.Transplantation. 1999; 67: 291-295Crossref PubMed Scopus (65) Google Scholar In renal transplant recipients with sickle cell disease, allograft sickling should be considered as a potential cause of an acute decline in function.

Centre for Nephrology and Department of Physiology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF and Department of Biochemistry, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK, Institute of Physiology and Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland and Department of Nephrology, University Hospital of Nice, 06000 Nice, France

Renal tubular acidosis is a metabolic acidosis due to impaired acid excretion by the kidney. Hyperchloraemic acidosis with a normal anion gap and normal (or near normal) glomerular filtration rate, and in the absence of diarrhoea, defines this disorder. However, systemic acidosis is not always evident and renal tubular acidosis can present with hypokalaemia, medullary nephrocalcinosis and recurrent calcium phosphate stone disease, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. Renal dysfunction in renal tubular acidosis is not always confined to acid excretion and can be part of a more generalised renal tubule defect, as in the renal Fanconi syndrome. Isolated renal tubular acidosis is more usually acquired, due to drugs, autoimmune disease, post-obstructive uropathy or any cause of medullary nephrocalcinosis. Less commonly, it is inherited and may be associated with deafness, osteopetrosis or ocular abnormalities. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. In vitro functional studies of these mutant proteins in cell expression systems have helped to elucidate the molecular mechanisms underlying renal tubular acidosis, which ultimately may lead to new therapeutic options in what is still treatment only by giving an oral alkali.

Long-acting calcium antagonists have been shown to be safe and effective in lowering blood pressure, both as first-line agents and in combination with other classes of antihypertensive drug. They have also been shown to reduce the incidence of cerebrovascular and cardiovascular events in elderly patients with predominantly systolic hypertension. It is clear that reduced morbidity and mortality in hypertension is related to the degree to which blood pressure is reduced, regardless of the therapy used. This is the single most important conclusion of all recent trials, especially in the sub-group of hypertensive patients with diabetes. The World Health Organization-International Society of Hypertension guidelines acknowledge this and do not make specific recommendations as to initial therapy in the absence of other medical factors. However the use of thiazide diuretics and beta-blockers has strong support from large placebo-controlled trials in patients with mild-moderate essential hypertension. The British Hypertension Society and JNC VI guidelines restrict their recommendations for the use of calcium antagonists to isolated systolic hypertension and angina, or when other agents have failed, are contraindicated or are not tolerated. However, their efficacy in lowering blood pressure, their tolerability and potentially beneficial secondary effect on proteinuria, especially in combination with an angiotensin-converting enzyme inhibitor, still make them attractive antihypertensive agents. The results of further long-term outcome trials that make direct comparisons between calcium antagonists and other classes of antihypertensive drug are still awaited. Unlike angiotensin-converting enzyme inhibitors, the antiproteinuric effect of calcium antagonists, even that of the non-dihydropyridine type, seems to depend on an adequate and stable reduction in blood pressure.