Bassam Alchi

What nephrologists need to know about antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies (aCL) and/or evidence of circulating lupus anticoagulant (LA). The kidney is a major target organ in both primary and secondary APS. With the expanding spectrum of renal diseases associated with APS, and the impact of APS in ESRD care, this subject is of increasing relevance to nephrologists. This review describes the various clinical manifestations and histological features of this syndrome, with reference to the kidney.

SM22α: The Novel Phenotype Marker of Injured Glomerular Epithelial Cells in Anti-Glomerular Basement Membrane Nephritis

Background/Aims: Our previous comprehensive analysis of the genes expressed in kidneys with anti-glomerular basement membrane (GBM) nephritis using DNA microarrays showed that SM22α was one of the highly expressed genes. SM22α is a 22-kDa cytoskeletal protein that is exclusively expressed in smooth muscle cells. We investigated the localization of SM22α at mRNA and protein levels, and its pathological significance in anti-GBM nephritis kidneys. Methods: Northern blot analysis, in situ hybridization, immunohistochemistry and double immunofluorescence studies were performed. The specific antibody (Ab) against SM22α was obtained by immunization of rabbits with recombinant rat SM22α protein. Results: SM22α mRNA expression was upregulated in kidneys and inducibly expressed in the parietal and visceral glomerular epithelial cells in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22α Ab showed that SM22α protein was localized in the same series of cells. Double immunofluorescence with anti-SM22α and anti-glomerular cell markers demonstrated that SM22α might be expressed in epithelial cells of injured glomeruli. In visceral epithelial cells, SM22α might be expressed in cells in which podocyte specific markers, podocalyxin and nephrin were lost. Conclusion: The injured glomerular epithelial cells in anti-GBM nephritis might undergo structural and functional alterations, including the expression of a smooth muscle marker, SM22α.

A clinicopathological study on the long-term efficacy of tonsillectomy in patients with IgA nephropathy.

Our study evaluated the clinical efficacy of tonsillectomy on the long-term renal survival in patients with primary IgA nephropathy (IgAN). Forty-six patients underwent tonsillectomy, and 74 patients did not. The mean of follow-up duration of all patients was 197.0±29.3 months (61–339 months). The baseline clinical and histological data at renal biopsy were not statistically different between the two groups with and without tonsillectomy. Five (10.9%) of the tonsillectomy group reached end stage renal failure (ESRF), whereas 19 (25.8%) of the non-tonsillectomy group did. The chi-square test between the two groups showed a significant difference (p<0.05). The renal survival of the tonsillectomy group was significantly higher than that of the non-tonsillectomy group by the Kaplan-Meier method with log-rank test (p<0.05). The Cox regression model also revealed that tonsillectomy had a significant favorable impact on the renal survival in long-term follow-up duration (p<0.05). Although our study was done by retrospective analyses, all the results proved that tonsillectomy had significant favorable effects on the long-term renal survival in patients with IgAN.

Renovascular hypertension: a unique cause of unilateral focal segmental glomerulosclerosis.

A 48-year-old man presented with malignant hypertension and massive proteinuria. Renal angiography showed complete obstruction of the left renal artery and 99mTc-mercaptoacetylglycine (MAG3) renography showed a nonfunctioning left kidney. Percutaneous transluminal renal angioplasty of the left renal artery was unsuccessful; hence, the patient underwent left nephrectomy because of uncontrolled hypertension and proteinuria. Histological examination of a right kidney specimen revealed lesions of focal segmental glomerulosclerosis with benign nephrosclerosis. In contrast, histology of the left kidney showed typical ischemic kidney with hypertrophy of arteriolar smooth muscle cells. The patient responded favorably to the nephrectomy, as his blood pressure and urinary protein dramatically decreased with no antihypertensive medication. This case illustrates the heterogeneous effect of the renin-angiotensin system on either kidney in patients with renovascular hypertension due to unilateral renal artery stenosis.

Mortality Predictors after 10 Years of Dialysis: A Prospective Study of Japanese Hemodialysis Patients

BACKGROUND This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with >10 yr of prior HD at study enrollment (n = 391) and those with < or =10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately. RESULTS In patients with >10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with < or =10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD. CONCLUSIONS Providing adequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for >10 yr.

Leiomyosarcoma of the abdominal aorta : A rare cause of renovascular hypertension

We describe the case of a 44-year-old woman who presented with renovascular hypertension caused by primary leiomyosarcoma of the abdominal aorta that had metastasized into the renal arteries. Despite an extensive radiological evaluation, the diagnosis was mistaken first for Takayasus arteritis and then for retroperitoneal hematoma or neoplasm. The patient developed renal failure due to bilateral renal infarction, and died 3 months after her initial presentation with ischemic colitis. Postmortem examination confirmed the diagnosis.

The morphological compensatory change of peritubular capillary network in chronic allograft rejection

Abstract:  To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 ± 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non‐pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non‐pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non‐pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.

A case of nephrotic syndrome 11 yr post-kidney transplantation

Abstract:  We present here a male patient who had developed nephrotic syndrome 11 yr after kidney transplantation. Nephrotic syndrome suddenly occurred after severe sunburn he got in Hawaii. Such a clinical course seemed very rare in kidney transplantation, and multifactorial etiology was suspected. The histological findings of graft biopsy were intricate. On light microscopy, there were mesangial expansion and endocapillary proliferation with duplication of GBM and crescent formation. Deposits of IgM in mesangium were the most prominent finding on immunofluorescence microscopy, but IgA and C3 deposits were also detected. Electron microscopy revealed paramesangial and a few subepithelial dense deposits. Additionally, small organized deposits were found in the subepithelial space. Based on these findings, a provisional diagnosis of IgA nephropathy superimposed on chronic transplant glomerulopathy was made. However, hepatitis C virus related nephropathy could not be excluded.