The relationship between chikungunya virus and the kidneys: A scoping review.

Several atypical forms of chikungunya fever (CHIK) have been described, including neurological, cardiac and renal involvement. These forms may be related to high morbidity and mortality rates. This scoping review based on the PubMed, Scopus, and WOS databases aims to identify and summarise all the available evidence regarding the clinical and histopathological presentations and risk factors associated with kidney injury related to CHIK, as well as the clinical impact. Thus, a total of 54 papers were selected from 1606 initial references after applying the defined inclusion criteria. Data on the association between kidney injury and CHIK are scarce, with studies only conducted in the acute phase of the disease, lacking further characterisation. Kidney injury incidence in hospitalised patients using the Kidney Disease Improving Global Outcomes criteria varies from 21% to 45%, being higher among patients with atypical and severe manifestations. Although acute kidney injury does not seem to be related to viraemia, it may be related to higher mortality. Few studies have described the renal histopathological changes in the acute phase of CHIK, with prevalent findings of acute interstitial nephritis with mononuclear infiltrate, glomerular congestion and nephrosclerosis. Only one study assessed the kidney function of patients in the subacute and chronic phases of CHIK. Additionally, individuals with comorbidities, including chronic kidney disease, may be among those with a greater risk of presenting worse outcomes when affected by CHIK. The results described herein may contribute to better understand the relationship between the kidneys and chikungunya virus.

Chikungunya virus as a trigger for different renal disorders: an exploratory study.

INTRODUCTION: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever. METHODS: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers. RESULTS: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group. CONCLUSIONS: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely.

Lupus Nephritis Class IV-Global Is Associated with a Higher Risk of End-Stage Renal Disease than Class IV-Segmental.

INTRODUCTION: The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) divides class IV into segmental and global (IV-S and IV-G) based on evidence suggesting different renal outcomes. However, subsequent studies have shown conflicting results. OBJECTIVE: This study was performed to compare long-term renal outcomes between the IV-S and IV-G classes. METHODS: This is a retrospective cohort study of adult patients with biopsy-proven class IV LN using the ISN/RPS classification. The primary end point was end-stage renal disease (ESRD). RESULTS: Among the 89 patients, rapidly progressive glomerulonephritis was twice as frequent in the IV-G group (60 vs. 29%; p = 0.005) than that in the IV-S group. Moreover, the IV-G group had a higher rate of biopsy with cellular and fibrocellular crescents (70.9 vs. 47.1%, p = 0.024) and more crescentic glomerulonephritis (34.5 vs. 5.8%, p = 0.007) than the IV-S group. After a mean follow-up of 57 months, the IV-G group had a greater risk of ESRD (RR 3.9; 95% CI 1.2-12.2, p = 0.006) than the IV-S group. Multivariate analysis indicated that class IV-G was an independent predictor of ESRD. CONCLUSIONS: Patients with class IV-G have a higher risk of ESRD than patients with class IV-S.

Effect of a Single Apolipoprotein L1 Gene Nephropathy Variant on the Risk of Advanced Lupus Nephritis in Brazilians.

OBJECTIVE: Apolipoprotein L1 gene (APOL1) G1 and G2 renal risk alleles (RRA) are associated with endstage renal disease in blacks with lupus nephritis (LN). The present study determined frequencies of APOL1 RRA in nonwhite Brazilian patients with LN and controls to assess association with renal outcomes. METHODS: APOL1 RRA were genotyped in 222 healthy blood donors (controls) and 201 cases with LN from 3 outpatient clinics. Two single-nucleotide polymorphisms in the G1 (rs73885319 and rs60910145) and an indel for the G2 (rs71785313) variant were genotyped. RESULTS: The frequency of APOL1 RRA in nonwhite Brazilian LN cases did not differ significantly from healthy controls, and few participants had 2 RRA. In the sample, 84.6% of LN cases and 84.2% of controls had 0 RRA, 13.4% and 15.3% had 1 RRA, and 2.0% and 0.4% had 2 RRA, respectively. LN cases with ≥ 1 APOL1 RRA had similar baseline characteristics and renal responses to treatment, yet faced higher risk for progressive chronic kidney disease (CKD) to an estimated glomerular filtration rate < 30 ml/min/1.73 m2 compared to those with 0 RRA (11.2% with 0, 29.6% with 1; 50% with 2 RRA, p = 0.005). Although glomerular lesions and activity scores on initial kidney biopsy did not differ significantly between individuals based on APOL1 genotype, chronicity scores, tubular atrophy, and interstitial fibrosis were more severe in those with ≥ 1 RRA (p = 0.011, p = 0.002, p = 0.018, respectively). CONCLUSION: Although initial kidney lesions and treatment responses were similar, a single APOL1 RRA in nonwhite Brazilians with LN was associated with increased risk of advanced CKD and possibly more tubulointerstitial damage.

Mannose-Binding Lectin2 Gene Polymorphism and IgG4 in Membranous Nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) has been linked to the lectin pathway, IgG4 and genetic susceptibility. We investigated the frequency of mannose-binding lectin2 (MBL2) gene polymorphisms and the serum ratio of IgG4 in patients with membranous nephropathy (MN). METHODS: Polymorphisms in the exon 1 of the MBL2 gene (codons 52, 54, and 57) and single base polymorphisms at positions -550 (HL) and -221 (XY) in the promoter region were evaluated in 60 patients compared to a control group (CG) of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing 2 etiologies of MN: idiopathic (35 patients) and secondary to systemic lupus erythematosus (25 patients). RESULTS: Patients with MN had a 2.54-fold higher probability (95% CI 1.51-4.31) of carrying the O alelle, exon 1 variant, and 11.16-fold higher probability (95% CI 4.77-28.41) of having A/O genotype when compared to CG. The frequency of polymorphisms in the promoter region was similar between the groups. Combined genotypes generally related to the defective production of MBL (YA/O, XA/O and O/O) were more frequent in patients with MN (OR 7.11; 95% CI 2.69-21.27), when compared to controls. The median of serum ratio IgG4 was 5% for idiopathic MN and 3% for lupus MN patients (p = 0.016). CONCLUSIONS: Our data suggests that MBL2 polymorphisms may be associated with the activation of the lectin pathway by IgG4 subclass antibodies in MN.

Comparative analysis of primary and secondary glomerulopathies in the northeast of Brazil: data from the Pernambuco Registry of Glomerulopathies - REPEG.

INTRODUCTION: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. OBJECTIVE: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). METHODS: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. RESULTS: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. CONCLUSION: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.

Comparative analysis of primary and secondary glomerulopathies in the northeast of Brazil: data from the Pernambuco Registry of Glomerulopathies - REPEG / Análise comparativa de glomerulopatias primária e secundária no nordeste do Brasil: dados do Registro Pernambucano de Glomerulopatias - REPEG

Abstract Introduction: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. Objective: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). Methods: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. Results: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. Conclusion: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.

Resumo Introdução: No Brasil, glomerulopatias são a terceira causa de doença renal crônica terminal, responsáveis por 11% dos pacientes em diálise. Entretanto, estudos sobre a prevalência desta patologia no nordeste do Brasil são escassos. Objetivo: O objetivo foi descrever os achados das biópsias e analisar comparativamente a apresentação clínico laboratorial entre as glomerulopatias primárias (GP) e as glomerulopatias secundárias (GS). Métodos: Estudo retrospectivo, realizado em dois hospitais públicos de ensino do estado de Pernambuco, nordeste do Brasil. Resultados: Foram avaliadas 1.151 biópsias, de 1998 a 2016. A amostra foi composta por 670 biópsias de rins nativos, após exclusão de patologias extra glomerulares e materiais inadequados. GP foram mais frequentes do que GS (58% × 42%). Dentre as GP, houve predomínio de glomeruloesclerose segmentar e focal (GESF). Glomerulonefrite membranoproliferativa e glomerulopatia colapsante foram responsáveis por 9% e 3% das GP, respectivamente. Das GS, as etiologias principais foram nefrite lúpica (67%) e infecciosas (10%). Sexo feminino, hematúria e nível elevado de creatinina estiveram relacionadas a uma maior chance de GS na análise multivariada. Síndrome nefrótica foi mais comum dentre as GP, já anormalidades urinárias e síndrome nefrítica prevaleceram nos pacientes com GS. Conclusões: Este é o primeiro registro de glomerulopatias do nordeste do Brasil. Demonstrou-se também uma análise comparativa das principais alterações clínico laboratoriais das GP e GS, com classificações atualizadas das doenças glomerulares.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis.

OBJECTIVE: The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. RESULTS: In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis

OBJECTIVE: The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. RESULTS: In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

Prevalence of persistent proteinuria in stable HIV/AIDS patients and its association with HIV nephropathy.

Human immunodeficiency virus (HIV)-related glomerular disease is a cause of end-stage renal disease, though there is no recent data from Brazil concerning this syndrome. Persistent proteinuria (PPt) is the main marker for glomerular disease, especially levels above 1.5 g. We examined the prevalence of and associated risk factors for PPt, along with the prevalence of HIV-associated nephropathy (HIVAN) among AIDS patients. We interviewed 411 patients who were attended at the HIV/AIDS section of the Clinical Hospital of the Federal University of Pernambuco (Brazil) from January through June 2004. PPt was defined as a positive urine dipstick exam on at least two occasions. The analyzed risk factors were: black race, a low CD4 lymphocyte count (<200 cells/mm(3)), an HIV RNA level of >100,000 copies/mL and patients on highly-active antiretroviral therapy (HAART). The patients were classified according to urinary protein/creatinine ratio (Up/Uc) < 1.0, 1.0-3.0 and > 3.0. Patients with Up/Uc >3.0 were submitted to renal biopsy. Among the 411 HIV/AIDS patients, the mean age was 37 years, 70% were male, 37.5% were black, the mean CD4 count was 363 cells/mm(3) (+/- 95), the mean RNA HIV count was 44,475 copies/mL (+/- 40,369), and 92% were on HAART. The prevalence of PPt was 5.6% (95% CI = 3.6 to 8.3%), and it was significantly associated with a low CD4 lymphocyte count (p<0.048). HIVAN was found in just one patient, and two patients improved after HAART.

Prevalence of persistent proteinuria in stable HIV/AIDS patients and its association with HIV nephropathy

Human immunodeficiency virus (HIV)-related glomerular disease is a cause of end-stage renal disease, though there is no recent data from Brazil concerning this syndrome. Persistent proteinuria (PPt) is the main marker for glomerular disease, especially levels above 1.5 g. We examined the prevalence of and associated risk factors for PPt, along with the prevalence of HIV-associated nephropathy (HIVAN) among AIDS patients. We interviewed 411 patients who were attended at the HIV/AIDS section of the Clinical Hospital of the Federal University of Pernambuco (Brazil) from January through June 2004. PPt was defined as a positive urine dipstick exam on at least two occasions. The analyzed risk factors were: black race, a low CD4 lymphocyte count (<200 cells/mm³), an HIV RNA level of >100,000 copis/mL and patients on highly-active antiretroviral therapy (HAART). The patients were classified according to urineary protein/creatinine ratio (Up/Uc) < 1.0, 1.0-3.0 and > 3.0. Patients with Up/Uc >3.0 were submitted to renal biopsy. Among the 411 HIV/AIDS patients, the mean age was 37 years, 70 percent were male, 37.5 percent were black, the mean CD4 count was 363 cells/mm³ (± 95), the mean RNA HIV count was 44,475 copies/mL (± 40,369), and 92 percent were on HAART. The prevalence of PPt was 5.6 percent (95 percent CI = 3.6 to 8.3 percent), and it was significantly associated with a low CD4 lymphocyte count (p<0.048). HIVAN was found in just one patient, and two patients improved after HAART.