Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Thrombotic microangiopathy in patients with malignant hypertension.

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.

Low Incidence of Acute Antibody-Mediated Rejection after HLA Desensitization in Living Donor Kidney Transplant Recipients.

Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.

Does Prior Abdominal Surgery Influence Peritoneal Transport Characteristics or Technique Survival of Peritoneal Dialysis Patients?

INTRODUCTION: Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. METHODS: Following an observational, retrospective design, we studied 171 incident PD patients, with the main objective of analyzing the influence of prior abdominal surgical procedures (main study variable) on baseline and evolutionary peritoneal transport characteristics (main outcome) and PD patient and technique survival (secondary outcomes). Abdominal surgeries were categorized according to the degree of presumed injury to the peritoneal membrane. We also considered the additive effect of aggressions to the membrane during the first year on PD therapy. RESULTS: All patients had a baseline peritoneal equilibration test with complete drainage at 60', and 113 patients had a second study at the end of the first year. Sixty-one patients (35.7%) had a record of prior abdominal surgery, including 29 patients with at least one major intraperitoneal surgery, 22 having undergone minor intraperitoneal procedures, and 21 with a background of major abdominopelvic extraperitoneal surgery. We did not observe differences, at baseline or after 1 year, among patients with or without previous abdominal procedures regarding small solute transport, overall capacity of ultrafiltration, free water transport, small pore ultrafiltration, or peritoneal protein excretion. Stratified analysis, considering prior and first-year-on-PD peritoneal aggressions, did not reveal any differences, although in this case our analysis was hampered by a limited statistical power. Abdominal surgical events did not influence patient or PD technique survival. CONCLUSION: Prior abdominal surgical procedures do not appear to compromise peritoneal membrane function or technique survival in patients successfully started on PD.

Long-term trends in the incidence of peritoneal dialysis-related peritonitis disclose an increasing relevance of streptococcal infections: A longitudinal study.

BACKGROUND: The selective impact of strategies for prevention of PD-related peritonitis (PDrP) may have modified, in the long term, the causal spectrum, clinical presentation and outcomes of these infections. OBJECTIVES: To compare trends in the incidence of PDrP by different microorganisms during a 30-year period, with a particular focus on streptococcal infections. To analyze the clinical presentation and outcomes of these infections. Secondarily, to investigate how the isolation of different species of streptococci can influence the clinical course of PDrP by this genus of bacteria. METHOD: Following a retrospective, observational design we investigated 1061 PDrP (1990-2019). We used joinpoint regression analysis to explore trends in the incidence of PDrP by different microorganisms, and compared the risk profile (Cox), clinical presentation and outcomes (logistic regression) of these infections. MAIN RESULTS: Our data showed a progressive decline in the incidence of PDrP by staphylococci and Gram negative bacteria, while the absolute rates of streptococcal (average annual percent change +1.6%, 95% CI -0.1/+3.2) and polymicrobial (+1.8%, +0.1/+3.5) infections tended to increase, during the same period. Remarkably, streptococci were isolated in 58.6% of polymicrobial infections, and patients who suffered a streptococcal PDrP had a 35.8% chance of presenting at least one other infection by the same genus. The risk profile for streptococcal infections was comparable to that observed for PDrP overall. Streptococcal PDrP were associated with a severe initial inflammatory response, but their clinical course was generally nonaggressive thereafter. We did not observe a differential effect of different groups of streptococci on the clinical presentation or outcome of PDrP. CONCLUSIONS: Time trends in the incidence of PDrP by different microorganisms have granted streptococci an increasing relevance as causative agents of these infections, during the last three decades. This behaviour suggests that current measures of prevention of PDrP may not be sufficiently effective, in the case of this genus of microorganisms.

Analysis of Factors Influencing the Prognostic Significance of Hyponatremia in Peritoneal Dialysis Patients.

BACKGROUND: The evidence linking low serum sodium levels with the risk of mortality in peritoneal dialysis (PD) patients is controversial. Considering the different mechanisms contributing to hyponatremia in these patients, it is conceivable that the prognostic significance of this factor may vary, according to the clinical setting. METHODS: Following a retrospective, observational design, we analyzed the association between hyponatremia and mortality in 748 patients incident on PD. We applied multivariate strategies of analysis, with the main objective of identifying subgroups of patients in whom hyponatremia could sustain different degrees of association with mortality (main outcome variable). For this purpose, we performed preliminary analyses to: (1) disclose predictors of serum sodium levels before and after (mean of first 3 months) initiation of PD (main study variable) and (2) investigate the overall prognostic significance of hyponatremia, in our patients. RESULTS: Comorbidity, hypoalbuminemia, and lower glomerular filtration rate (GFR) were main predictors of hyponatremia. Use of icodextrin was another inverse correlate of serum sodium, and the only consistent predictor of a decline of natremia, once PD was started. Multivariate analysis confirmed early hyponatremia as an independent marker of survival. However, stratified analyses showed that this association was most apparent in specific subsets, namely, hypoalbuminemic, more anemic patients with higher baseline levels of GFR and C-reactive protein and faster peritoneal solute transport rates. Other factors potentially reinforcing the prognostic significance of hyponatremia included lower lean body mass levels, nonprescription of renin-angiotensin-aldosterone system antagonists, and use of icodextrin-based PD solution. On the contrary, baseline overhydration or categorization by classic predictors of mortality (age, comorbidity, diabetes) did not appear to influence the risk pattern associated with lower serum sodium levels. CONCLUSIONS: Our results suggest that hyponatremia performs as a consistent correlate of the risk of mortality mainly in PD patients manifesting direct or indirect signs of inflammation and wasting, while this association is not apparently linked to the presence of overhydration or nominal, preexisting comorbid conditions.