Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach.

Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.

Genetic testing in focal segmental glomerulosclerosis: in whom and when?

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.

User-centred design for developing e-Health system for renal patients at home (AppNephro).

BACKGROUND: Despite the promising benefits of the e-Health approaches (including provide technology-based healthcare services to anyone, anytime, and anywhere), few solutions are adopted in daily practice. User acceptance is one of the major obstacles that hinder the success of technology approaches. End-users often stress misalignments among their problems and the solutions that technology systems aim to solve. In other cases, systems developed are unfriendly or unadjusted to the daily practice of clinicians or patient's life. To maximize user acceptance, the relevance of adopting user-centred design and development techniques is well-known. However, users are often assumed to be a homogeneous group with the same set of requirements, what leads to an ineffective identification and addressment of user requirements. Furthermore, usability and accessibility issues must be carefully addressed to guarantee also the right alignment of solutions with user needs. OBJECTIVE: to develop an e-Health system for renal patients at home by adopting user-centred design practices, usability and accessibility standards. MATERIAL AND METHODS: users were categorized in four different groups (i.e., digital patients/caregivers, non-digital patients/caregivers, clinicians and nurses) and a sample was included in the design and development team. Questionnaires and interviews were used to identify user requirements and assess prototypes. RESULTS: Requirements were considered for every kind of user, what resulted on a multi-faceted e-Health system implying different technologies and functionalities regarding to each target user. CONCLUSION: Identification and continuous involvement of all kind of users allow their needs to be properly understood and addressed by technology, raising user acceptance of the final product.

Advanced chronic renal failure (ACRF) study. Baseline characteristics, evaluation of the application of the structured information for the election of renal replacement therapy and one-year evolution of the incident patients in the ACRF medical office. / Estudio ERCA. Características basales, evaluación de la aplicación de la información estructurada para la elección de tratamiento renal sustitutivo y evolución a un año de los pacientes incidentes en la consulta ERCA.

BACKGROUND AND OBJECTIVES: Analyze evolution Renal Chronic Failure stage 4-5 (ACRF) patients and influence information they receive (educational process, EP) in modality Renal Replacement Therapy (RRT) or conservative treatment (CT) in multidisciplinar ACRF Office. MATERIAL AND METHODS: Prospective, multicenter study (3 centers). Inclusion: from June-01-2014 to October-01-2015; observation: 12 months or until start RRT or death if they occur before 12 months; ends October-01-2016. RESULTS: 336 patients were included (60% males), median and intercuartile rank 71.5 (17), 55% ≥ 70 years; Follow up initiation eGFR CKD-EPI: 21 (9) ml / min / 1.73m2; Charlson Index (ChI) with / without age 8 (3) / 4 (2); Diabetic patients: 52,4%. The EP was carried out in 168, eGFR 15 (10) ml / min / 1.73m2. The initial treatment election: 26% peritoneal dialysis (PD), 45% hemodyalisis (HD), 26% CT, kidney trasplant 3%; 60 patients started RRT: 3.3% kidney traspant; 30% PD, 66% HD; 104 admissions in 73 patients, the most frequent cause: cardiovascular disease (42%). Fallecimiento: 23 patients (6.8%). Age was higher (78.4 (6) vs. 67.8 (13.4), P<.001), higher ChI 9.8 (2.1) vs. 7.4 (2.5), P<.001). All deceased who received EP had chosen CT; 61% of deceased had at least one hospital admission vs. 39% alive (P<0.001). Cox regression: age and Charlson index were the predictive mortality variables. CONCLUSIONS: The population of ACRF patients is elder, comorbid, with high rate hospitalizations rate. The PD election is higher than usual. The EP has been very useful tool and has favored the PD choice.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Peritoneal dialysis fluid biocompatibility impact on human peritoneal membrane permeability.

BACKGROUND: We have compared the effects of conventional lactate-based peritoneal dialysis fluid (CPDF) with respect to bicarbonate/lactate-based fluid on peritoneal ultrafiltration (UF) and peritoneal permeability, and on variations on gene expression in cells isolated from effluents of patients' peritoneal bags. METHODS: This was a non-randomized sequential prospective study including all incident peritoneal dialysis (PD) patients (n = 40) recruited in our centre. Peritoneal equilibration tests (PETs) were performed using CPDF or BPDF both containing 2.27% glucose during a 48-h interval in four different sequences. Gene expression variation of selected genes was measured by reverse transcription polymerase chain reaction in mesothelial cells obtained from the total drained fluid during the PET. RESULTS: In the overall study, the use of BPDF was associated with significantly lower mass transfer area coefficient for urea and creatinine, longer accelerated peritoneal examination test times for urea and creatinine, lower total pore area available for exchange over diffusion distance and lower UF. There were no differences in the gene expression of aquaporins 1-3, endothelial and inducible nitric oxide synthase (NOS3 and NOS2), or interleukin-6. The SNAIL and E-CADHERIN gene expression normalized ratio was evaluated in peritoneal effluents of cells obtained from CPDF and BPDF. We observed that the SNAIL/E-CADHERIN mRNA ratio decreased when the dialysis sequence started with BPDF and went on to CPDF, but not when the sequence was the opposite. CONCLUSION: This study shows that those patients who started PD treatment with BPDF were characterized by a better biocompatibility profile. BPDF associates with lower peritoneal permeability to small molecules and lower UF.

Anaemia and fever in Kidney transplant. The role of human parvovirus B19. / Anemia y fiebre en el postrasplante renal: su relación con el parvovirus humano B19.

Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

Renal Replacement Therapy: Purifying Efficiency of Automated Peritoneal Dialysis in Diabetic versus Non-Diabetic Patients.

BACKGROUND: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD), a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF) in patients on peritoneal dialysis (PD) is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD) patients, with end-stage renal disease (ESRD) secondary to diabetic nephropathy (DN) in comparison to non-diabetic nephropathy (NDN), using different PD solutions in combination. DESIGN: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. RESULTS: The fraction of renal urea clearance (Kt) relative to distribution volume (V) (or total body water) (Kt/V), or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl) decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively), and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively). Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0.22, 12 months 1.63 ± 0.39, 24 months 1.73 ± 0.47; NDN: baseline 1.59 ± 0.40, 12 months 1.76 ± 0.47, 24 months 1.80 ± 0.46), in order to maintain the net water balance. The daytime dwell contribution, the fraction of day and the renal fraction of studies parameters provide sustained benefit in the follow-up time, above 30%. CONCLUSIONS: The wet day and residual renal function are determinants in the achievement of the objective dose of dialysis, as well as in the water and sodium balance. The cause of chronic kidney disease (CKD) does not seem to influence the cleansing effectiveness of the technique.

Water overload as a biomarker for heart failure and acute renal failure.

Heart failure (HF) and acute renal failure (ARF) are two very prevalent entities in our environment which impact directly and synergistically in the morbidity and mortality of our patients. ARF, when oligoanuric, often leads to water overload. It represents the precipitating core of the mechanism of acute decompensation of the HF and is associated with the worsening of symptoms, hospitalisation and death. Determining the water balance in HF can be complex and depends, largely, on the underlying pathophysiology. New biomarkers and new technologies are proving to be useful for the detection and identification of risk of acutely decompensated HF that may allow early intervention and reversal of the ARF that translates into better clinical outcomes.

The occurrence or fibrillary glomerulonephritis in patients with diabetes mellitus may not be coincidental: a report of four cases.

Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45-50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed.