Patricia Malafronte

Association of the MCP-1 −2518 A/G Polymorphism and No Association of Its Receptor CCR2 −64 V/I Polymorphism with Lupus Nephritis

Objective. To evaluate whether the A/G polymorphism at position −2518 in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) or the V/I polymorphism at position −64 of the receptor, CCR2, are associated with lupus nephritis (LN) or any clinical characteristics of the disease or with renal survival in a patient population. Methods. We selected 197 patients with lupus nephritis and 220 matched healthy controls for study. MCP-1 and CCR2 genotyping was performed by polymerase chain reaction. Clinical and laboratory data were compiled from patients’ charts over followup that ranged from 6 months to 10 years. Results. The G/G genotype of MCP-1 was more common in LN patients (p = 0.019), while the A allele was associated with healthy controls (p = 0.007) as was the V allele of CCR2 (p = 0.046) compared to LN patients. Clinical index measures [SLE Disease Activity Index (SLEDAI)], immunological markers, renal histology, renal function at enrollment, and renal survival were not influenced by these polymorphisms. A less aggressive renal disease, measured by renal SLEDAI index, was associated with the V allele of the CCR2 gene polymorphism. Conclusion. These findings support that MCP-1 −2518 G/G is associated with LN but there was no association of this genotype with renal function or renal survival. When studying CCR2 −64 V/I polymorphism we showed a positive association of the V allele with healthy controls but no association of the genotype with LN patients.

MYH9 and APOL1 Gene Polymorphisms and the Risk of CKD in Patients with Lupus Nephritis from an Admixture Population

MYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95%CI 1.47–9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95%CI 1.2–3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.

Evaluation of neutrophilic activity in patients submitted to kidney transplantation

Background: Cryoglobulinemia is frequent in renal transplant patients. The mononuclear and polymorphonuclear neutrophil (PMN) phagocytic systems are important for the clearance of cryoglobulin immune complexes. There might be a reduced phagocytic activity in transplant patients with cryoglobulinemia (CRYO+). Methods: We studied the phagocytic activity by PMNs, in the presence of immune complexes in renal transplant patients, with or without hepatitis C virus (HCV) infection. Thirty-seven patients subjected to kidney transplant were evaluated, and for the control group, healthy blood donors were chosen. The presence of cryoprecipitate was evaluated, as well as HCV infection, phagocytic activity by neutrophils during the ingestion and digestion phase. Results: The presence of cryoprecipitate was detected in 75.7% of the patients, 39.28% of which had HCV infection. IgG, IgM, IgA, and C3 and C4 complement components were identified in the cryoprecipitate. There was a reduction in the ingestion phase of phagocytosis by PMNs in renal transplant CRYO+ though the digestion phase was preserved. Conclusion: We concluded that there was a decreased PMN activity in transplanted patients presenting cryoglobulinemia.

Prevalence of hypovitaminosis D and the different-dose cholecalciferol supplementation effects on renal transplant recipients

High prevalence of hypovitaminosis D has been observed in patients with chronic kidney disease. However, there is not much data about its prevalence in kidney transplant recipients (KTRs). The study included 83 adult KTRs at a single center to calculate the prevalence of hypovitaminosis D. Among the 83 patients, those with incomplete data were excluded leaving 22 patients available for study. The demographic and biochemical data were analyzed retrospectively. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), phosphorus, calcium, and creatinine were evaluated. The 22 selected patients were divided into two groups: (1) those who received 10,000 IU of cholecalciferol orally per week, and (2) those who received 10,000-20,000 IU/week. The Vitamin D level rate was calculated to evaluate the time necessary to reach serum values ≥30 ng/mL. Hypovitaminosis D was present in 80.7% (67/83) of the patients. Eleven patients received 10,000 IU/week of cholecalciferol, and the other 11 patients received 10,000-20,000 IU/week (approximately 64,000 IU/month). The calcium, phosphorus, and PTH values did not show any differences between the two groups. We estimate that a dose of approximately 64,000 IU/month of cholecalciferol was sufficient to reach values of ≥30 ng/mL of 25(OH)D in approximately 2.1 months in the insufficient and 4.3 months in Vitamin D-deficient patients. The prevalence of hypovitaminosis D was high among Brazilian KTR, and low-level doses of cholecalciferol (approximately 64,000 IU/month) were sufficient to control hypovitaminosis D.

Outcomes in renal transplant recipients with lupus nephritis: experience at a single center

Abstract Background: The long-term prognosis of renal transplant recipients with systemic lupus erythematosus is still controversial. The outcome of these patients depends on the population studied, race/ethnicity, socioeconomic conditions, donor-related factors and recurrent lupus nephritis (LN), among other factors. Objective: This study was conducted to evaluate kidney transplantation outcomes for adult Brazilian patients with LN at a single center. Subjects and method: The archival records of all patients with LN who had received a kidney transplant at Santa Casa of Sao Paulo Hospítal were reviewed. Kaplan–Meier method was used to determine the survival rate. Results: We identified 18 patients with LN subjected to 22 kidney transplants during the 20-year interval. Two patients received three renal grafts. The majority of the patients were female, with 33.7 ± 10 years at the time of the transplantation, and half of them were African descendants or mixed. Sixteen transplants were performed from deceased donors and six from living-related donors. The patient survival rate was 90%, and graft survival was 68% at 10 years. Chronic allograft nephropathy was the major cause of graft loss. Two patients developed extra-renal manifestations of lupus. There was no clinical or histological evidence of recurrent LN. Conclusion: Renal transplantation is a method which can provide a long-term survival for patients with SLE and end-stage renal disease.

Cryoglobulinemia in Chronic Hemodialysis Patients

Abstract Background: Renal failure patients submitted to chronic hemodialysis can present with cryoglobulinemia. There are few studies on cryoglobulins in chronic hemodialysis patients. The aim of the present study was to determine the prevalence and to identify the components of cryoglobulins in chronic hemodialysis patients. Methods: Fifty-four patients on chronic hemodialysis were evaluated for the presence of cryoglobulins, after inclusion and exclusion criteria. The components of the cryoprecipitate were analyzed. Results: Cryoglobulins were detected in 83% (45/54) of the patients on chronic hemodialysis. The cryoprecipitate was constituted by IgG, IgM, IgA, and complement fractions C3 and C4. Conclusion: We concluded that there was a high prevalence of cryoglobulins in chronic hemodialysis patients, and the cryoprecipitate was constituted by IgG, IgM, IgA, and complement fractions C3 and C4.