Family studies point to an important genetic element in the genesis of diabetic nephropathy, but it is not known whether renal abnormalities are present prior to the onset of diabetes. To address this issue we examined all consecutive patients suffering from type II diabetes with a duration of more than 10 years who attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307 did not. All offspring who were phenotypically normal (no hypertension, normal oral glucose tolerance, non-smoking) and agreed to participate were examined, 26 from nephropathic and 30 from non-nephropathic diabetic parents. They were compared with 30 offspring matched for age, gender and BMI from non-diabetic parents as controls. We measured urinary albumin excretion under baseline conditions and at several time points after ingestion of 300 g cooked beef and submaximal treadmill exercise, respectively. In addition, casual blood pressure, ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were measured. Primary renal disease was excluded by clinical examination. Under baseline conditions, median urinary albumin excretion rate (AER; microgram/min) was significantly (P < 0.005) higher in offspring of nephropathic type II diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non-nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4; 0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional increase of AER in offspring of nephropathic type II diabetics (median 16-fold) than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls (4.8-fold). In offspring of nephropathic diabetic patients casual and particularly ambulatory systolic blood pressures were significantly higher, but AER was not correlated with blood pressure. In summary, higher values, albeit within the normal range, for baseline and postexercise albuminuria were noted in phenotypically normal offspring of parents with type II diabetes and nephropathy. The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.

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In insulin-dependent diabetes mellitus (IDDM) elevated exchangeable sodium (Na) levels are found even in the absence of hypertension, but it is not known whether this is associated with increased sensitivity of blood pressure to sodium level. To clarify this issue we compared 30 patients with IDDM (19 without and 11 with microalbuminuria, i.e. more than 30 mg albumin/day) and 30 control subjects matched for age, gender and body mass index. The subjects were studied on the 4th day of a low-salt diet (20 mmol/day) under in-patient conditions and were subsequently changed to the same diet with a high-salt supplement, yielding a total daily intake of 220 mmol Na/day. Circadian blood pressure, plasma renin activity (PRA), plasma atrial natriuretic factor (p-ANF), plasma cyclic guanosine 5'-phosphate (p-cGMP) and urinary albumin were measured. The proportion of salt-sensitive subjects, i.e. showing increment of mean arterial pressure > or = 3 mmHg on high-salt diet, was 43% in diabetic patients (50% of diabetic patients with and 37% without microalbuminuria) and 17% in control subjects (p < 0.05). Lying and standing PRA levels on low- or high-salt diet were significantly lower in diabetic patients than in control subjects. Salt-sensitive diabetic patients had significantly higher lying ANF on high-salt (38.7 +/- 4.2 pmol/l vs 20.1 +/- 2.3 pmol/l, p < 0.005) than on low-salt diet. The results suggest that (i) the prevalence of sodium sensitivity is high in IDDM (ii) sodium sensitivity is found even in the absence of nephropathy as indicated by albuminuria.

Introduction The vital renal replacement therapy makes it impossible for dialysis patients to distance themselves socially. This results in a high risk of SARS-CoV-2 infection and developing COVID-19 with excess mortality due to disease burden and immunosuppression. We determined the efficacy of a 100 µg booster of mRNA-1273 (Moderna, Inc., Cambridge, Massachusetts, USA) 6 months after two doses of BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) in 194 SARS-CoV-2 naïve dialysis patients. Methods Anti-SARS-CoV-2-spike antibodies were measured with the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH, Germany) 4 and 10–12 weeks after two doses of BNT162b2 as well as 4 weeks after the mRNA-1273 booster. The presence of neutralizing antibodies was measured by the SARS-CoV-2 Surrogate Virus Neutralization Test (GenScript Biotech, USA). Two different cut-offs for positivity were used, one according to the manufacturer's specifications and one correlating with positivity in a plaque reduction neutralization test (PRNT). ROC analyses were performed to match the anti-SARS-CoV-2-spike antibody cut-offs with the cut-offs in the surrogate neutralization assay accordingly. Results Any level of immunoreactivity determined by anti-SARS-CoV-2-spike antibody assay was found in 87.3% (n = 144/165) and 90.6% (n = 164/181) 4 and 10–12 weeks after two doses of BNT162b2. This was reduced to 68.5% or 60.6% 4 weeks and 51.7% or 35.4% 10–12 weeks, respectively, when using the ROC revealed cut-offs for neutralizing antibodies in the surrogate neutralization test (manufacturer given cut-off ≥ 103 U/ml and cut-off correlating with PRNT ≥ 196 U/ml). Four weeks after the mRNA-1273 booster, the concentration of anti-SARS-CoV-2-spike antibodies increased to 23 119.9 U/ml and consecutively to 97.3% for both cut-offs of neutralizing antibodies. Conclusion Two doses of BNT162b2 followed by one dose of mRNA-1273 within 6 months in patients receiving maintenance dialysis resulted in significant titers of SARS-CoV-2-S-Ab. While two doses of mRNA vaccine only achieved adequate humoral immunity in a minority, the third vaccination boosts the development of virus-neutralizing quantities of SARS-CoV-2 spike antibodies (against wild type SARS-CoV-2) in almost all patients.

In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.