Saowanee Yenrudi

Renal pathology and HIV infection in Thailand.

The existence of a human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) as a distinct disease entity characterized by glomerulosclerosis is well established in North America and Western Europe. Although the large number of HIV-infected cases overwhelm the Asian countries, no cases of HIVAN are documented in the literature. We studied 26 cases of HIV-infected Thai patients with proteinuria greater than 1.5 g/d of protein during 1995 and 1996. None of the patients were treated with antiretroviral drugs at the time of renal biopsy. Intravenous drug addiction and sexual transmission were risk factors in 11 and 15 patients, respectively. Pathological examinations were performed by light microscopic and immunoperoxidase study. Mesangial proliferative glomerulonephritis was found in 17 cases, immunoglobulin A (IgA) nephropathy in 2 cases, and diffuse proliferative glomerulonephritis and interstitial nephritis secondary to cryptococcal infection in 2 cases each. One case each had membranous glomerulopathy, membranoproliferative glomerulonephritis, and granulomatous interstitial nephritis secondary to tuberculosis. The renal pathological findings of HIVAN with the unique features described in previous literature were not evident in these patients. Although the data in this study are limited to 26 HIV-infected Thai patients, we believe that HIVAN is uncommon in the Asian HIV-infected population.

PERITUBULAR CAPILLARY FLOW DETERMINES TUBULOINTERSTITIAL DISEASE IN IDIOPATHIC NEPHROTIC SYNDROME

The spatial relationship between renal perfusion and nephronal structure was determined in 51 nephrotic patients consisting of 11 patients with steroid sensitive, minimal change (MC) nephrosis, 12 patients with steroid resistant, mesangial proliferative (MesP) nephrosis and without tubulointerstitial fibrosis (TIF), 11 patients with steroid resistant, MesP nephrosis and with low grade TIF and 17 patients with focal segmental glomerulosclerosis (FSGS). The intrarenal hemodynamic study revealed a unique correlation between renal perfusion and nephronal structure. A normal or slight reduction in peritubular capillary flow observed in MC or mild MesP nephrosis correlates with an intact tubulointerstitial structure. A moderate reduction in peritubular capillary flow observed in steroid resistant, MesP nephrosis induces a low incidence of TIF. A severe reduction in peritubular capillary flow denotes a higher incidence of TIF as that observed in nephrosis with FSGS. Thus, it is of notion that the reduction in renal perfusion precedes the development of tubulointerstitial fibrosis and thereby supports the concept of renal perfusion as a crucial determinant of nephronal structure.

Glomerular Endothelial Dysfunction Determines Disease Progression: A Hypothesis

A glomerular endothelial function with its hemodynamic impact is proposed to determine disease progression. In the clinical settings associated with an intact endothelial function, such as minimal-change steroid-sensitive nephrosis, the early phase of diabetes mellitus and the early stage of an experimental model of renal ablation in animals, it was observed that adequate renal perfusion correlates with the intact structure and function of the nephron with no evidence of disease progression. In contrast, the clinical settings associated with endothelial dysfunction, such as chronic glomerulonephropathy, the late stage of diabetes mellitus and a renal ablation model in animals, are usually associated with a reduction in renal perfusion. The magnitude of renal hypoperfusion observed in all forms of chronic glomerulonephropathies is proportional to the degree of clinical severity. A progressive pattern of renal hypoperfusion is uniquely observed when disease severity progresses. In this context, a new therapeutic maneuver aiming to improve renal perfusion is proposed for treating glomerulonephropathy with disease progression and preventing it from developing to end-stage renal disease.

Reduced endothelial factor VIII staining in renal microcirculation correlates with hemodynamic alteration in nephrosis

Endothelial factor VIII staining in renal microcirculation was performed in eight nephrotic patients associated with mesangial proliferation (MesP) and six nephrotic patients associated with focal segmental glomerulosclerosis (FSGS). The result in MesP revealed a greater staining for glomerular endothelial factor VIII (35 ± 15%) and for postglomerular capillary endothelial factor VIII (65 ± 21%) than that observed in FSGS, which revealed a 11 ± 8% staining for glomerular endothelial factor VIII and 19 ± 15% staining for postglomerular capillary endothelial factor VIII. This finding implies that there is a greater loss of endothelial cell in renal microcirculation in FSGS. Such a finding correlates with the intrarenal hemodynamics which illustrated (Futrakul, P.; Sitprija, V.; Yenrusi, S. Glomerular endothelial dysfunction determines disease progression: a hypothesis. Am. J. Nephrol. 1997, 17, 533–540.) a mild reduction in renal plasma flow (535 ± 106 mL/min/1.73 m2, normal 600 mL/min/1.73 m2) and in peritubular capillary flow (422 ± 80 mL/min/1.73 m2, normal 480 mL/min/1.73 m2) in MesP and (Futrakul, P. Coagulation in glomerulonephritis and nephrotic symdrome: Its therapeutic intervention. In Asian Manual of Nephrology, Takeuchi, T.; Sugino, N.; Ota, K., Eds.; SEAMIC Publication, Tokyo, 1981; pp. 89–95.) a greater reduction in renal plasma flow (108 ± 50 mL/min/1.73 m2) and in peritubular capillary flow (87 ± 42 mL/min/1.78 m2) in FSGS. Therefore the study has emphasized both the structural and functional defects of endothelium in renal microcirculation in particular in FSGS.

A CORRELATION BETWEEN RENAL MORPHOLOGY AND RENAL CIRCULATION IN PEDIATRIC NEPHROTIC SYNDROME

A morphometric analysis of the renal biopsy specimens and intrarenal hemodynamic study were performed in 37 pediatric patients with idiopathic nephrotic syndrome. The study indicated an inverse correlation between intrarenal hemodynamics (renal plasma flow and peritubular capillary flow) and a relative area of renal cortical interstitium. In respect to the glomerular study, the incidence of glomerulosclerosis increased as the renal perfusion decreased, however, the correlation did not reach a statistical significance.

Potassium depletion in a healthy north-eastern Thai population: No association with tubulo-interstitial injury

SUMMARY:  Potassium depletion prevails among the healthy population of north‐east Thailand, as well as among patients with certain metabolic disorders such as upper urinary tract stones, the sudden unexplained death syndrome, distal renal tubular acidosis and hypokalaemic periodic paralysis. However, definite proof of the relationship of potassium depletion and these metabolic disorders is lacking. We prospectively studied muscle and kidney potassium content including renal tissue pathology in three groups of healthy adult Thai subjects who died of vehicular accidents. Group 1 (n = 24) were Bangkok city dwellers; groups 2 (n = 10) and 3 (n = 22) lived in north‐eastern Thailand in the metropolitan area and in the villages, respectively. The muscle potassium content of group 1 (338.5 ± 9.6 mEq/kg dry weight (DW)) were similar to group 2 (307.9 ± 11.9 mEq/kg DW), but was greater than group 3 (295.4 ± 9.1 mEq/kg DW; P < 0.01). The kidney potassium content of group 1 (208.6 ± 7.8 mEq/kg DW) was significantly higher than group 3 (175.9 ± 6.3 mEq/kg DW, P < 0.05). In group 3, the muscle potassium correlated linearly with the kidney potassium (r = 0.455, P = 0.33). None of the group 3 patients had renal histopathological change compatible with a diagnosis of focal or diffuse interstitial nephritis.This study confirms that potassium depletion is common among healthy rural dwellers in north‐east Thailand. This deficit was probably chronic. However, there was minimal renal tubulo‐interstitial change.

Consultants for the American Journal of Nephrology 1997

Consultants for the American Journal of Nephrology 1997 Abrass, Christine Adler, Sharon Agodoa, Lawrence Akmal, Mohammad Anderson, Sharon Andreucci, Vittorio Avram, Morel Bakris, George Balow, James Bennette, William Boswell, William Breyer, Julia Langman, Craig Levin, Nathan Limb, Victoria Maroni, Bradley Martinez-Maldonado, Manuel Matthew, Weir R. Mitch, William Mushnick, Robert Nissenson, Allan Nolph, Karl Nosrati, Saeid