Eculizumab treatment for rescue of renal function in IgA nephropathy

Background

Immunoglobulin A (IgA) nephropathy is a chronic glomerulonephritis with excessive glomerular deposition of IgA1, C3 and C5b-9, which may lead to renal failure.

Case Diagnosis/Treatment

We describe the clinical course of an adolescent with rapidly progressive disease leading to renal failure in spite of immunosuppressive treatment. Due to refractory disease the patient was treated with eculizumab (anti-C5) for 3 months in an attempt to rescue renal function. Treatment led to clinical improvement with stabilization of the glomerular filtration rate and reduced proteinuria. Discontinuation of treatment led to a rapid deterioration of renal function. This was followed by a single dose of eculizumab, which again reduced creatinine levels temporarily.

Conclusions

Early initiation of eculizumab therapy in patients with progressive IgA nephropathy may have a beneficial effect by blocking complement-mediated renal inflammation.     

Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients

Purpose

The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial.

Methods

A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m² or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan–Meier method and Cox models.

Results

One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points.

Conclusion

Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.     

Higher Incidence of Renal Allograft Glomerulonephritis in Living-Related Donor Kidney Transplantation

Glomerulonephritis recurrence has emerged as one of the leading causes of allograft loss. We aimed to investigate the effect of living-related and deceased donation on the incidence of renal allograft glomerulonephritis and its effect on renal allograft survival.

Increased chymase-positive mast cells in children with crescentic glomerulonephritis

Mast cell-derived chymase is an angiotensin II-forming enzyme that appears to be involved in tubulointerstitial fibrosis in the kidneys. Previous studies have shown that the level of chymase increases in grafted kidneys after rejection and in adult patients with diabetic nephropathy. However, the significance of chymase in children with renal diseases has not been investigated. Using immunohistochemistry, we have investigated chymase expression in biopsy samples of renal tissue from 104 children with kidney diseases, including rapidly progressive crescentic glomerulonephritis (n?=?3), diabetic nephropathy (n?=?2), allografted kidney (n?=?3), membranoproliferative glomerulonephritis (n?=?6), immunoglobulin A nephropathy (n?=?33) and Henoch–Schönlein purpura nephritis (n?=?23). Increased numbers of chymase-positive mast cells were observed in the renal cortex of all three patients with crescentic glomerulonephritis (mean 26.0/mm²; range 19.3–36.8/mm²). Chymase-positive cells were also observed in the renal biopsy of an allografted kidney and in those from children with diabetic nephropathy. The mean number of chymase-positive cells in renal tissue samples characterized by each renal disease was significantly correlated with the mean intensity of the interstitial fibrosis in that same tissue sample (Spearman’s rank correlation test p?=?0.0013; rank correlation coefficient ?0.84). These findings suggest that mast cell-derived chymase plays an important role in juvenile crescentic glomerulonephritis.     

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

Despite almost universal implementation of renoprotective therapies over the past 25 years, the risk of end-stage renal disease (ESRD) in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of extensive studies that we have been conducting on the patients attending the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. The etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the loss of glomerular filtration rate, not reduction of albumin excretion rate, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better still, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD.     

Dialysis-treated end-stage kidney disease in Libya: epidemiology and risk factors

Purpose

End-stage kidney disease (ESKD) is now a worldwide pandemic. In concert with this, ESKD in Libya has also increased exponentially in recent decades. This review aims to define the magnitude of and risks for this ESKD epidemic among Libyans as there is a dearth of published data on this subject.

Methods

A systematic review was conducted by searching PubMed, EMBASE and Google scholar databases to identify all relevant papers published in English from 2003 to 2012, using the following keywords: end stage, terminal, chronic, renal, kidney, risk factors, Arab, North Africa and Libya.

Results

In 2003, the reported incidence of ESKD and prevalence of dialysis-treated ESKD in Libya were the same at 200 per million population (pmp). In 2007, the prevalence of dialysis-treated ESKD was 350 pmp, but the true incidence of ESKD was not available. The most recent published WHO data in 2012 showed the incidence of dialysis-treated ESKD had risen to 282 pmp and the prevalence of dialysis-treated ESKD had reached 624 pmp. The leading causes of ESKD were diabetic kidney disease (26.5 %), chronic glomerulonephritis (21.1 %), hypertensive nephropathy (14.6 %) and congenital/hereditary disease (12.3 %). The total number of dialysis centers was 40 with 61 nephrologists. Nephrologist/internist to patient ratio was 1:40, and nurse to patient ratio was 1:3.7. Only 135 living-related kidney transplants had been performed between 2004 and 2007. There were no published data on most macroeconomic and renal service factors.

Conclusions

ESKD is a major public health problem in Libya with diabetic kidney disease and chronic glomerulonephritis being the leading causes. The most frequent co-morbidities were hypertension, obesity and the metabolic syndrome. In addition to provision of RRT, preventive strategies are also urgently needed for a holistic integrated renal care system.     

Occurrence of anti-C1q antibodies in IgA nephropathy

Background: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. Methods: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n=36) and SLE nephritis (n=37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulo-nephritis (n=7) and minimal change disease (n=2), in which circulating immune complexes are usually not present, and in 40 healthy controls. Results: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P<0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P<0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. Conclusions: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.     

Impact of Posttransplantation Glomerulonephritis on Long-term Outcome of Kidney Transplants: Single-Center 20-Year Experience

Background

Successful renal transplantation has been performed in patients with end-stage renal disease and has been routine in patients with end-stage renal failure for more than two decades. Despite advances in the use of immunosuppressants, there has been only modest improvement in long-term allograft survival. Accumulating data have demonstrated that chronic rejection and recurrent glomerulonephritis are major causes of long-term allograft loss. However, data regarding the long-term impact of posttransplantation glomerulonephritis (PTGN) on ethnic Chinese populations are still unavailable.

Methods

From 1984 to 2010, a total of 268 patients who underwent renal allograft biopsies were reviewed retrospectively. Renal outcomes were compared by Kaplan–Meier analysis, and risk factors for renal survival and all-cause mortality were analyzed using the Cox proportional hazards model.

Results

In all, 85 patients (31.7 %) had PTGN, and the mean time of disease onset was 5.32 ± 5.18 years after transplantation. Among the 85 PTGN cases, 33 (39 %) were immunoglobulin A (IgA) nephropathy, 24 (28 %) were focal segmental glomerulosclerosis, and 8 (9.4 %) were membranous GN. Significant risk was associated with posttransplant IgA GN in hepatitis B virus carriers (odds ratio 5.371, 95 % confidence interval 1.68, 17.19; p = 0.0064). A total of 45 PTGN patients had allograft loss, of whom 49 % had IgA nephropathy. Patients with PTGN had inferior allograft survival rates compared to those with other pathologic findings (p < 0.0003).

Conclusions

Taken together, our results indicate that PTGN had a strong negative impact on long-term kidney graft survival. Posttransplant IgA nephropathy is a leading cause of allograft loss in Chinese kidney transplant patients with PTGN.     

Clinicopathological characteristics and outcomes of pediatric patients with systemic small blood vessel vasculitis

Background

Systemic small blood vessel vasculitis (SSV) is uncommon among pediatric patients, and the predictive value of the new histopathological classification for SSV in terms of renal outcomes in these patients is unknown.

Methods

The study cohort comprised 38 pediatric patients and 285 adult patients with SSV who were treated in a medical center between 1993 and 2012.

Results

Children accounted for 11.8 % of all patients with SSV diagnosed during the study period. In contrast to the adult patients, the pediatric patients were predominantly female (73.7 vs. 51.9 %; P?P?P?ESRD) among pediatric patients (hazard ratio?2.273, P?ESRD was highest in pediatric patients with the sclerotic glomerulonephritis subtype, followed by the mixed, crescentic and focal glomerulonephritis subtypes (in descending order of probability) (P?Conclusions Estimated histopathological classification has a prognostic value for renal outcome and response to therapy in children with SSV.     

Clinico-pathological correlations of congenital and infantile nephrotic syndrome over twenty years

Background

Nephrotic syndrome (NS) presenting early in life is caused by heterogeneous glomerular diseases. We retrospectively evaluated whether histological diagnosis in children presenting with NS in the first year of life predicts remission or progression to end-stage kidney disease (ESKD).

Methods

This is a single centre retrospective review of all children diagnosed with NS before one year of age between 1990 and 2009. All subjects had a renal biopsy, which was independently blindly reviewed by a single renal pathologist for the purpose of this study.

Results

Forty-nine children (25 female) who presented at 0.1–11.6 (median 1.6) months were included with 31 presenting within the first three months of life. Histopathological review diagnostic categories were; 13 Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic complications of the biopsy. Eight children achieved remission (four MesGN, one Finnish type changes, one FSGS, one MCD and one membranous) with patient and renal survival of 73 % and 43 %, respectively, at follow-up duration of 5–222 (median 73) months (with five lost to follow-up). All children with Finnish-type histopathological changes presented within five months of age. Due to the historical nature of the cohort, genetic testing was only available for 14 children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1 and one ITGA3) with none of these nine children achieving remission. All of them had presented within four months of age and required renal replacement therapy, and two died.

Conclusions

Histopathological findings are varied in children presenting with NS early in life. Whilst groups of histological patterns of disease are associated with differing outcomes, accurate prediction of disease course in a specific case is difficult and more widespread genetic testing may improve the understanding of this group of diseases and their optimal management     

Reduced podocin expression in minimal change disease and focal segmental glomerulosclerosis is related to the level of proteinuria

Background

Glomerular podocyte molecules are involved in the pathogenesis of congenital nephrotic syndrome. However, their role in primary nephrotic syndrome is not clear. This study investigated the expression of nephrin, podocin and synaptopodin in primary nephrotic syndrome.

Methods

Eighty-seven patients with primary nephrotic syndrome including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis Type I (MPGN) were included in the study. Glomerular expression of nephrin, podocin and synaptopodin was studied in renal biopsies by immunofluorescence and immunohistochemistry. Correlation of expression with clinical and biochemical parameters was performed.

Results

The pattern of expression for all podocyte proteins in controls was uniform fine granular along the capillary walls towards the visceral epithelial cell aspect. Glomerular expression of nephrin was present in all renal biopsies and was similar to that in controls. Glomerular synaptopodin expression was seen in all MN and MPGN patients, while it was seen in 74 % (17/23) MCD and 93.5 % (29/31) FSGS. Reduced synaptopodin expression showed no correlation with clinical and biochemical factors. Podocin expression was present in 5/23 MCD (22 %), 3/31 FSGS (9.6 %), 13/17 MN (76.4 %) and 13/16 MPGN (81 %) patients. The reduced expression of podocin significantly correlated with the degree of proteinuria (p = 0.032). No correlation with age, gender and serum creatinine level was observed.

Conclusion

Reduction of glomerular podocin expression found in MCD and FSGS is related to the amount of proteinuria. Our findings suggest that alteration in podocyte phenotype may not be a primary event and may reflect the degree of podocyte injury in primary nephrotic syndrome.     

Long-term renal outcome in pediatric glomerulonephritis associated with crescent formation

Background

Information on long-term renal outcome of pediatric glomerulonephritis associated with crescent formation is limited. A single center retrospective study was conducted to assess long-term renal survival and to determine whether the 2010 classification for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis can predict renal outcome in pediatric glomerulonephritis associated with crescent formation.

Methods

Biopsy and clinical data of children, aged ≤ 18 years with ≥ 10 glomeruli and ≥ 10% crescentic glomeruli during January 1998 to December 2015, were reviewed. Biopsies were classified according to the 2010 classification into focal, crescentic, mixed, and sclerotic classes. The clinical endpoint was end-stage renal disease (ESRD).

Results

Of 72 children, 14 patients (19.4%) had positive ANCA. The biopsy indication was rapidly progressive glomerulonephritis in 38 patients (52.8%) and 22 patients (30.6%) required dialysis at onset. Lupus nephritis was the most common diagnosis (43.1%), followed by IgA nephropathy/Henoch–Schoenlein purpura (HSP) (22.2%). ESRD occurred in 18 patients (25%) and the risk of ESRD differed among the histological classifications (p < 0.001). Dialysis at onset and sclerotic class was independent predictors of ESRD in an adjusted model. The risk of ESRD was four-fold higher in patients requiring dialysis at onset and 7.7-fold higher in sclerotic patients than in crescentic patients.

Conclusions

The probability of ESRD was substantial in pediatric glomerulonephritis associated with crescent formation. The 2010 classification is useful for establishing long-term renal prognosis. Future research is required to validate whether histological classification could be a determinant in therapeutic guideline modification, since long-term renal prognosis is different in each class.

     

Detection of Mature Macrophages in Urinary Sediments: Clinical Significance in Predicting Progressive Renal Disease

The ability to predict the rate of progression of renal parenchymal disease may help in its clinical management. We undertook characterization of urinary macrophages obtained from patients with various renal diseases paving special attention to the differentiation from non-progressive to progressive renal diseases. A total of 84 patients were divided into one of three categories. A highly progressive group included patients with rapidly progressive glomerulonephritis, diabetic nephropathy, membranoproliferative glomerulonephropathy, primary focal segmental sclerosis and diffuse proliferative lupus nephropathy, moderately progressive group included those with IgA nephropathy and Alport's syndrome and non progressive group included patients with thin basement membrane nephropathy, minimal change nephrotic syndrome, idiopathic renal hematuria and urolithiasis. Urinary sediments were reacted with four monoclonal antibodies (CD68/macrophages vimentin, cytokeratin, and 25F9/mature macrophages). In normal individuals mature macrophages (25F9⁺ cells) were absent in urinary sediments. The number of 25F9⁺ cells in the urine was highest in the highly progressive group, less prominent in the moderately progressive group, and virtually absent in the non progressive group. The 25F9⁺ cells reacted with anti-CD68 and anti vimentin antibody, whereas the 25F9⁺ cells did not react with anti-cytokeratin antibody. These findings indicate that the detection of mature macrophages in urine is useful to estimate the prognosis of renal parenchymal diseases and may help to differentiate some glomerular diseases (e.g., thin basement membrane disease vs. Alport's syndrome, and minimal change nephrotic syndrome vs. primary focal segmental sclerosis).     

C1q nephropathy in children: clinical characteristics and outcome

Background

C1q nephropathy has been suggested as a separate disease entity. C1q positivity has also been described in association with nephrotic syndrome (NS) as a potential marker for worse outcome. The aims of this study were to describe the clinical characteristics, laboratory parameters and outcomes of 35 children whose renal histology revealed predominant mesangial C1q deposition and to investigate if the experience at our institution supports the above hypothesis.

Method

Clinical and pathological characteristics of all children whose kidney biopsies showed positive C1q staining were retrospectively recorded. The outcome of children with minimal change nephrotic syndrome (MCNS) and predominant mesangial C1q deposition based on C1q staining was compared with that of a concurrent group of children with MCNS with no such immune staining.

Results

The median age of the patient cohort was 4.5 years (range 6 months to 16 years), 69 % were boys and 88 % presented with nephrotic syndrome (NS). Children with C1q staining and MCNS had more relapses (p?=?0.001) and shorter relapse-free periods (p?=?0.033) than those with negative immunostaining, but the long-term outcomes were similar in both groups.

Conclusion

Our data do not support C1q nephropathy as a separate diagnostic category. Children with MCNS and mesangial C1q deposition (staining) showed more relapses but no difference in long term renal outcome.     

Do C1q or IgM nephropathies predict disease severity in children with minimal change nephrotic syndrome?

Background

It has been suggested that C1q and immunoglobulin M (IgM) nephropathy are variants of minimal change nephrotic syndrome (MCNS). Many researchers believe that these two conditions signify a worse prognosis for children with MCNS in comparison with immunofluorescence (IF)-negative MCNS. The aim of our study was to determine the prognostic significance of C1q nephropathy and IgM nephropathy in children with MCNS.

Methods

Fifty-five children with MCNS who had been biopsied over the course of 24 years at our institution were retrospectively categorized into three groups on the basis of IF microscopy findings: IF-negative MCNS (29/55 patients), MCNS with IgM nephropathy (19/55 patients), and MCNS with C1q nephropathy (7/55 patients). Clinical characteristics at disease presentation, clinical course, and renal outcome were compared between groups during the median follow-up period of 16.9 years (minimum 1.0, maximum 31.1 years).

Results

No statistically significant differences in clinical characteristics at disease presentation, clinical course, and renal outcome were found. Children with IgM nephropathy, C1q nephropathy, and IF-negative MCNS were clinically indistinguishable.

Conclusions

We concluded that C1q or IgM nephropathy variants do not seem to signify a worse prognosis in children with MCNS in comparison with IF-negative MCNS.     

Immediate and long-term high levels of plasma homocysteine after extracorporeal shock wave lithotripsy in patients with renal stone disease

Background

Plasma homocysteine levels increase in patients with chronic renal failure. Numerous studies have demonstrated that kidney function is one of the most important determinants of plasma total homocysteine (tHcy) concentration. In this study we aimed to evaluate the relationship between tHcy levels and extracorporeal shock wave lithotripsy (ESWL) for patients with renal stones and to see if the change in homocysteine levels continued if renal dysfunction improved.

Materials and methods

The study consisted of 20 patients who underwent first-time ESWL for renal stones. Every patient gave 3 blood samples at 24 h before surgery and at 2 days and at 3 months after ESWL for measurement of plasma levels of tHcy, creatinine, vitamin B₆, and vitamin B₁₂.

Results

The 20 patients (12 male, 8 female) had a mean age of 42.8 ± 11.7 years. tHcy levels showed a statistically significant increase from 9.4 ± 1.4 to 18 ± 4.8 and 11.2 ± 2.1 at 2 days and at 3 months, respectively. Serum creatinine also showed a statistically significant increase compared to baseline at 2 days and at 3 months after ESWL.

Conclusion

After first-time ESWL, the increase in serum levels of creatinine and tHcy due to renal injury, such as ischemia/reperfusion injury, may be severe and continue for a long period, such as 3 months. According to baseline levels, the increase in homocysteine levels as an indicator of oxidant stress was more severe than the creatinine levels after ESWL for renal stones. Our patients were first-time ESWL patients; however, in patients who undergo EWSL more than once long-term high tHcy levels should also be considered as renal.     

Studies on Hanganutziu-Deicher antibodies in renal diseases]

H-D antibodies which were known as antibodies detectable in patients with serum sickness have recently been detected in renal diseases. We attempted to detect IgG, IgA and IgM antibodies to N-glycolyl GM3, among other H-D antibodies, by ELISA in various renal diseases and found increased IgM antibody in mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, IgA nephropathy, minimal change nephrotic syndrome and Henoch-Sch?nlein purpura nephritis (HSPN), elevated IgA antibody in IgA nephropathy and HSPN and raised IgG antibody in IgA nephropathy. In 2 cases of IgA nephropathy, there was noted a good correlation between clinical course and anti-N-glycolyl GM3 antibody titers. Measurement by ELISA of IgG antibody to cytomegalovirus (CMV) seemed as one of immune pathogenetic factors of IgA nephropathy showed a high positive rate for this antibody of IgA nephropathy patients and a positive correlation between the antibody and anti-N-glycolyl GM3 antibody. The key molecule of H-D antigens is N-glycolyl neuraminic acid (NGNA) and this sialic acid does not normally exist in humans. One can surmise, therefore, that in those renal diseases in which there was noted an elevation of anti-N-glycolyl GM3 antibody, this antigen is formed or generated by some unknown mechanism. In other words, it may be that humans are not entirely negative for H-D antigens but have a minimum inherent antigenicity and a potential capacity to synthesize these antigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digital subtraction venography in the diagnosis of renal vein thrombosis.

Fifteen cases of renal vein thrombosis were seen in patients with nephrotic syndrome, both adult and pediatric, and all had kidney biopsies. Six patients were found to have membranoproliferative glomerulonephritis, 3 membranous nephropathy, 2 focal segmental glomerulosclerosis, 2 renal amyloidosis and one each minimal change disease and diffuse mesangial proliferative glomerulonephritis. The diagnosis of renal vein thrombosis was made in all patients by utilizing digital subtraction venography. This method is simple, safe, noninvasive and quite efficient.     

Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation

Purpose

The aim of this study was to investigate the effect of renal cortex transient receptor potential melastatin 7 (TRPM7) suppression on renal ischemia reperfusion injury induced by transplantation in mice.

Methods

M7shRNA was used to decrease the expression of TRPM7 in NRK-52e cells. The mice were subjected to renal intra-parenchymal injection with lentivirus containing M7shRNA to produce hypo-expression of TRPM7 in renal cortex. Cell hypoxia mode and syngeneic renal transplantation in vivo were established. Then the effects of M7shRNA were measured by fluorescent probe for reactive oxygen species (ROS), intracellular calcium and magnesium; Western blot was applied for p38-MAPKs and Bax expression in cell studies. In vivo studies, mice were killed 24 h, 48 h, 72 h, 7 days and 21 days, respectively, after transplantation and the kidneys were dissected. Serum creatinine was measured, and the H&E, Masson’s trichrome staining, TUNEL, Kim-1 and α-smooth muscle actin were used to evaluate pathological change.

Results

In cell model of hypoxia, the level of ROS in NRK-52e-M7shRNA was significantly lower than that in both NRK-52e and NRK-52e control cells, while the activation of p38-MAPKs was limited. In renal transplanted mice, renal function of M7shRNA group was conspicuously better than PBS- and vector-control-treated group. The histological examination showed that renal tubule injury and interstitial fibrosis were lower in M7shRNA-treated group compared with PBS and vector-control group.

Conclusions

Suppression of renal cortex TRPM7 could alleviate kidney injury induced by transplantation in mice. The mechanism may involve reducing the early stage of ischemia reperfusion injury by inhibition of intracellular Ca²⁺, Mg²⁺ and ROS.     

The renal pathological findings in Japanese HIV-infected individuals with CKD: a clinical case series from a single center

Background

Chronic kidney diseases (CKD) have emerged as a significant cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). However, the detailed study of renal pathological findings currently remains unclear in these Japanese patients.

Methods

A retrospective cohort study was undertaken to investigate renal pathological findings between January 1996 and July 2016. Our study included 20 Japanese HIV-infected patients with CKD; 10 cases had undergone renal biopsies, and 10 cases had undergone autopsies, respectively. Moreover, in the 10 biopsied patients, their clinical courses as well as renal outcomes after renal biopsy were also reviewed.

Results

All of the patients had received combination antiretroviral therapy (cART). The 10 biopsy cases (mean age, 54 ± 14 years and duration of cART, 8 ± 5 years) included three cases of diabetic nephropathy (DMN), two of IgA nephropathy, two of cART-induced tubulointerstitial nephritis (TIN), one of minimal change disease, one case of only finding intrarenal arterioles, and one case without abnormal findings. Among those patients, their clinical courses were preferable except for in the DMN cases. In the autopsy cases (mean age, 52 ± 10 years and duration of cART, 5 ± 5 years), no distinct mesangial or membranous abnormalities were detected. Mild to moderate tubulointerstitial atrophies were observed in six cases. Intrarenal arteriosclerosis was identified in nine cases, and the proportion of global glomerulosclerosis seen was 8.4 ± 12.5%/100 glomeruli.

Conclusion

DMN and cART-induced TIN was noted in the biopsy cases. In the autopsy cases, renal arteriosclerosis, global glomerulosclerosis, and tubulointerstitial atrophy were remarkable. Early diagnosis of kidney diseases should be crucial to introduce optimal management, including controlling rigorous comorbidities and appropriate use of cART, to prevent further progression of CKD.