COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome: case report and review of the literature.

BACKGROUND: Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies. WDR73 pathogenic variants were described as the first genetic cause of GAMOS and, very recently, four novel causative genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. CASE PRESENTATION: We present the clinical and genetic characteristics of two unrelated infants with clinical suspicion of GAMOS who were born from consanguineous parents. Both patients showed a similar clinical presentation, with early-onset nephrotic syndrome, microcephaly, brain atrophy, developmental delay, axial hypotonia, and early fatality. We identified two novel likely disease-causing variants in the OSGEP gene. These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants. CONCLUSIONS: Our findings expand the spectrum of pathogenic variants in the OSGEP gene and, taken in conjunction with the results of the literature review, suggest that the OSGEP gene should be considered the main known monogenic cause of GAMOS. Early genetic diagnosis of GAMOS is of paramount importance for genetic counseling and family planning.

The effect of some medications given to CKD patients on vitamin D levels.

BACKGROUND: Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease (CKD) population. OBJECTIVES: To assess the clinical and analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL), including the possible role of associated drugs. METHODS: A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53.3%, mean age 70.8 [±16.1] years, mean GFR (MDRD-4) 43.6 [±25.5] ml/min/1.73 m²). 25-OH-D3 levels were collected in spring. Clinical and biochemical data and associated medications were recorded. RESULTS: Mean 25-OH-D3 levels were 8.23 [±4.03] ng/ml. Eighty-eight patients (64.7%) had 3 or more concomitant drugs. Only 7 patients (5.1%) were not receiving any medication. Patients were divided in three groups according the therapies into none (n=26), RAS inhibitors or allopurinol (n=81), and RAS inhibitors plus allopurinol (n=30); with the aim to study the influence of statin therapy. Patients under renin angiotensin (RAS) inhibitors or Allopurinol treatment presented significantly higher 25-OH-D3 levels (p=0.001 and p=0.01 respectively), however patients with Statins treatment had lower 25-OH-D3 level (p=0.039). Personal history of diabetes, cardiovascular events or other therapies did not modify 25-OH-D3 levels, adjusted by age and eGFR. CONCLUSIONS: CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25-OH-D3 levels, however those with statins treatment had lower vitamin D levels. Randomized controlled trials are required to confirm these findings.

Haematuria increases progression of advanced proteinuric kidney disease.

BACKGROUND: Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function. OBJECTIVE: To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up. RESULTS: The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73 m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73 m2/year, p<0.05), but not in patients >65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73 m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73 m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73 m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (ß=-4.316, p=0.025). CONCLUSIONS: The presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatment.

Assessment of nutritional status in haemodialysis patients.

BACKGROUND: Malnutrition is a common problem and a risk factor of mortality in haemodialysis patients. However, there is no consensus for its assessment. OBJECTIVE: To assess the relationship between nutritional status, measured by bioimpedance spectrometry (BIS), and laboratory markers of nutritional status, as well as nutritional evolution and its changes after 1 year. METHODS: We performed an observational prospective study on 124 haemodialysis patients (aged 61.2 ±[15.8] years, 62.9% were males, 33.1% were diabetic. Laboratory markers of nutritional status and BIS were implemented at baseline and after one year. RESULTS: At baseline, lean mass index (LMI) (13.3 [3.6] Kg/m2) was inversely correlated with age (P=.006), and directly with male gender (P=.01). At baseline, the fat mass index (FMI) (mean 11.2 & 6.1kg/m2) correlates directly with the body mass index (P<.001) and the female gender (P=.004). We found no association with comorbidity or inflammatory markers. We did not observe any correlation between lean mass or fat mass modifications and nutritional marker modifications. Patients with LMI gain (>0kg/m2) have lower baseline serum albumin (P=.017), lower baseline LMI (P<.001) and higher baseline FMI (P=.027). Patients with FMI loss (<0kg/m2) have lower systolic blood pressure (P=.04). CONCLUSIONS: Assessment of nutritional status through laboratory parameters does not have a good correlation with body composition parameters or with their modifications.

[Vitamin D deficiency in a Spanish cohort of patients with chronic kidney disease]. / Deficiencia de vitamina D en una cohorte española de pacientes con enfermedad renal crónica.

BACKGROUND AND OBJECTIVE: Vitamin D (25-OH-D3) deficiency is an emerging global health problem. Chronic kidney disease (CKD) patients have a higher risk of this deficiency. We aimed to determine the prevalence of 25-OH-D3 deficiency in a cohort of CKD patients in an urban area of Spain and its relationship with cardiovascular disease (CVD). PATIENTS AND METHODS: We evaluated the prevalence of 25-OH-D3 deficiency in 751 incident patients referred to our outpatient clinic (male gender 59.3%, mean age 67.2 [± 15] years, mean GFR (MDRD-4) 47.9 ± 25.5 ml/min/1.73 m(2)) with different stages of CKD. We excluded end stage renal disease patients and with kidney transplant. Clinical data and biochemical parameters related to bone and mineral metabolism were recorded. Levels of 25-OH-D3< 15 ng/ml were considered to be deficient. RESULTS: The mean 25-OH-D3 levels were 17.06 [± 12.93] ng/ml. Only 10% of our patients had adequate 25-OH-D3 levels (>30 ng/ml) and 51% showed deficient levels. 25-OH-D3 deficiency worsened with the progression of CKD (P<.05). Elderly people (P=.001), female gender (P=.02), and diabetes (P=.03) were closely associated with 25-OH-D3 deficiency. 25-OH-D3 deficiency was inversely associated with serum PTH (P=.02), and directly associated with serum calcium (P<.004). Patients with a history of CVD had lower 25-OH-D3 levels (P=.038). CONCLUSIONS: 25-OH-D3 deficiency has a high prevalence in CKD patients, and the severity increases with the progression of kidney disease. Elderly, women and diabetic patients have a higher risk of 25-OH-D3 deficiency. 25-OH-D3 deficiency was related to higher levels of PTH and lower serum calcium.

Factors related with the progression of chronic kidney disease.

BACKGROUND: Our aims were to determine the rate of progression of chronic kidney disease (CKD) and to identify predictors, with particular emphasis on bone and mineral metabolism. METHODS: Retrospective and observational study including 300 patients with advanced CKD (61.2% males, 33.1% diabetics; age 65.6±14 years). Mean follow-up time was 19.4±10.1 months. Baseline estimated glomerular filtration rate (eGFR) (MDRD-4) was 22.5±7.18 mL/min. To calculate the rate of decline in eGFR, we used the slope of the regression line between all determinations of eGFR and follow-up time. We calculated the mean values for proteinuria and serum phosphate, calcium, uric acid, and PTH, as well as 24-hour urinary excretion of urea nitrogen over time for each patient. Follow-up was at least 6 months and included at least 4 measurements of eGFR. RESULTS: The mean rate of decline eGFR (-1.64 mL/min/1.73 m²/year) was inversely correlated with serum phosphate levels (4.3±2.1 mg/dL, P<.001), PTH (256.3±193.7 ng/L, p<.001) and proteinuria (0.84±1.31 g/day, P=.004) and directly correlated with mean serum calcium (P<.001) and the presence of hypertension (P<.02). However, only serum phosphate, serum PTH, and proteinuria persisted as predictors in the multivariate analysis. Stable-GFR patients (positive slope) were older (P=.041) and had lower serum phosphate and PTH levels (P<.01 and P<.01 respectively) and lower proteinuria (P<.01). CONCLUSIONS: The rate of decrease in eGFR was correlated with serum phosphate and PTH levels and proteinuria. All of these factors can be modified with an adequate treatment.

Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial.

BACKGROUND: Pentoxifylline (PTF) is a potential therapeutic agent in chronic kidney disease due to its antiinflammatory and antiproteinuric effects that may influence the progression of renal disease. SUBJECTS AND METHODS: We conducted a prospective randomized trial of 91 patients with estimated glomerular filtration rate (eGFR) <60 ml/min, calculated with 4-variable Modification of Diet in Renal Disease (MDRD-4) Study equation. Patients were randomly assigned to treatment with PTF 400 mg (twice a day) (n=46) or to continue their usual therapy (n=45). Clinical, biochemical and inflammatory parameters were measured at baseline, and at 6 and 12 months of treatment. The objective of the study was to analyze the effect of PTF treatment on inflammatory markers and secondarily the effect on renal disease progression. RESULTS: Baseline characteristics were similar in the 2 groups. High-sensitivity C-reactive protein (hs-CRP), serum fibrinogen and TNF-alpha decreased significantly in patients treated with PTF in comparison with the control group at 12 months (p=0.002, p=0.001 and p=0.000, respectively). Median urinary albumin excretion did not decrease with PTF treatment. In the PTF group, there was no significant change in eGFR after 12 months (from 42.3 ± 10.2 to 44.7 ± 11.3 ml/min per 1.73 m(2)), whereas in the control group there was a worsening by the end of the study (from 40.1 ± 12.4 to 35.7 ± 13.4 ml/min per 1.73 m(2)) (p=0.000 between groups). CONCLUSIONS: PTF treatment decreases inflammatory markers in chronic kidney disease and stabilizes renal function.