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Background Novel mRNA-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended. A number of cases with de novo or relapsing glomerulonephritis shortly after vaccine application were reported, some of which presented with gross hematuria. Methods We collected 10 cases of macrohematuria following mRNA-based SARS-CoV-2 vaccination at our tertiary care institution and referring centers. Additionally we pooled all 25 published cases from the literature with ours to analyse their clinical characteristics. Results Most macrohematuria episodes (72.2%) began within 2 days after vaccination, the majority after the second dose. In some individuals, repeated episodes occured after subsequent doses of the same vaccine. 65.7% of patients never had macrohematuria before. 45.7% were known to suffer from IgAN, the rest had no prior renal diagnosis. IgAN was the most frequent new diagnosis but ANCA-associated vasculitis and anti-GBM disease were also identified. AKI occurred in 28.6% of patients, a rise in serum creatinine not meeting KDIGO AKI criteria in 28.6%. Treatment ranged from conservative management, RAAS-inhibitors, steroids and cyclophosphamide to plasmapheresis. While renal outcomes were mainly favourable in isolated IgAN, they were poor in patients with additional or isolated small vessel vasculitis. Conclusion Awareness of gross hematuria after SARS-CoV-2 vaccination is important. Close follow-up and additional work-up in particular in individuals without known underlying kidney disease or worsening renal function is essential. For patients with vaccine associated macrohematuria an alternative vaccine class might be considered for subsequent vaccinations.

BackgroundNephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known.MethodsThe NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo.The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response.DiscussionThe NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support.Trial registrationClinicalTrials.gov, NCT03057431. Registered on February 20 2017.

<b><i>Background:</i></b> Metabolic acidosis (MA) is a common complication in kidney transplantation (KTx). It is more prevalent in KTx than in CKD, and it occurs at higher glomerular filtration rates. The pathophysiologic understanding of MA in KTx and its clinical impact has been highlighted by few recent studies. However, no guidelines exist yet for the treatment of MA after KTx. <b><i>Summary:</i></b> MA in KTx seems to share pathophysiologic mechanisms with CKD, such as impaired ammoniagenesis. Additional kidney transplant-specific factors seem to alter not only the prevalence but also the phenotype of MA, which typically shows features of renal tubular acidosis. There is evidence that calcineurin inhibitors, immunological factors, process of donation, donor characteristics, and diet may contribute to MA occurrence. According to several mainly observational studies, MA seems to play a role in disturbed bone metabolism, cardiovascular morbidity, declining graft function, and mortality. A better understanding of the pathophysiology and evidence from randomized controlled trials, in particular, are needed to clarify the role of MA and the potential benefit of alkali treatment in KTx. Alkali therapy might not only be beneficial but also cost effective and safe. <b><i>Key Messages:</i></b> MA seems to be associated with several negative outcomes in KTx. A deeper understanding of the pathophysiology and clinical consequences of MA in KTx is crucial. Clinical trials will have to determine the potential benefits of alkali therapy.

BackgroundGraft survival after kidney transplantation has significantly improved within the last decades but there is a substantial number of patients with declining transplant function and graft loss. Over the past years several studies have shown that metabolic acidosis plays an important role in the progression of Chronic Kidney Disease (CKD) and that alkalinizing therapies significantly delayed progression of CKD. Importantly, metabolic acidosis is highly prevalent in renal transplant patients and a recent retrospective study has shown that metabolic acidosis is associated with increased risk of graft loss and patient death in kidney transplant recipients. However, no prospective trial has been initiated yet to test the role of alkali treatment on renal allograft function.MethodsThe Preserve-Transplant Study is an investigator-initiated, prospective, patient-blinded, multi-center, randomized, controlled phase-IV trial with two parallel-groups comparing sodium bicarbonate to placebo. The primary objective is to test if alkali treatment will preserve kidney graft function and diminish the progression of CKD in renal transplant patients by assesing the change in eGFR over 2 years from baseline. Additionally we want to investigate the underlying pathomechanisms of nephrotoxicity of metabolic acidosis.DiscussionThis study has the potential to provide evidence that alkali treatment may slow or reduce the progression towards graft failure and significantly decrease the rate of end stage renal disease (ESRD), thus prolonging long-term graft survival. The implementation of alkali therapy into the drug regimen of kidney transplant recipients would have a favorable risk-benefit ratio since alkali supplements are routinely used in CKD patients and represent a well-tolerated, safe and cost-effective treatment.Trial registrationClinicalTrials.gov NCT03102996. Trial registration was completed on April 6, 2017.