Pediatric kidney transplantation in Thailand: experience in a developing country.

From July 1996 to November 2006, 46 patients received kidney transplants at five pediatric centers in Thailand. The male-female ratio was 1.9:1. The primary causes of end-stage renal disease (ESRD) included hypoplastic or dysplastic kidney, chronic glomerulonephritis, reflux nephropathy, pyelo nephritis or interstitial nephritis, focal segmental glomerulosclerosis, and rapidly progressive glomerulonephritis. Mean (SD) age at onset of ESRD was 10.1 (3.1) years, and at transplantation was 11.1 (2.9) years. Preemptive transplantation was performed in 2 patients. Cadaveric donors were used in 67.4% of procedures. Induction of immunosuppression with interleukin (IL)-2 monoclonal antibody was used in 41.3% of the patients. At 1 year posttransplantation, maintenance therapy included corticosteroids in 100% of patients, cyclosporine in 81.6%, tacrolimus in 15.8%, azathioprine in 31.6%, and mycophenolate mofetil in 57.9%. Standardized height z scores at transplantation and last follow-up (mean [SD], 40.0 [28.3] months) remained the same at -1.9. Mean (SD) serum creatinine level at the last follow-up was 1.3 (0.8) mg/dL. Patient survival at 1 and 5 years was 96% and 88%, respectively. Graft survival at 1 and 5 years was 98% and 84%, respectively. The medical expenses at 1, 6, and 12 months were US$601, US$464, and US$384 per month, respectively. The Thai per gross domestic product per capita was US$758 per month. Medical expenses were paid by the government in 44.2% of cases, charity foundations in 39.5%, and the patients' parents in 16.3%. Although the causes, management, and outcomes of ESRD were not different from those in other countries, access to treatment and medical expenses may be substantial barriers in developing countries.

Tubular function and tubulointerstitial disease.

Tubular transport determined by the fractional excretion (FE) of filtered solutes was studied in 129 nephrotic patients; 72 patients with mesangial proliferation (MesP-NS) and intact tubulointerstitium (group 1), 13 patients with MesP-NS and superimposed tubulointerstitial fibrosis (TIF; group 2), 27 patients with mild focal segmental glomerulosclerosis (FSGS; group 3), and 17 patients with severe FSGS (group 4). In the 72 nephrotic patients with MesP-NS and normal tubulointerstitium (no TIF), tubular transport was intact (FE of sodium [FENa], 0.5 +/- 0.5; FE of calcium [FECa], 0.3 +/- 0.3; FE of phosphate [FEPO4], 14 +/- 13; FE of uric acid [FEUA], 9.8 +/- 5; FE of magnesium [FEMg], 1.3 +/- 0.5). In the 13 nephrotic patients with MesP-NS and superimposed TIF (4.9% +/- 2%), there was no difference in FE solutes from those in group 1 except for FEMg (3.3 +/- 0.9; P < 0.001). In the 27 nephrotic patients with mild FSGS (TIF, 28% +/- 9%), four of five variables of FE solutes (FENa, 1.2 +/- 0.7; P < 0.001; FECa, 0.9 +/- 0.8; P < 0.001; FEPO4, 17 +/- 12; P, not significant; FEUA, 16.5 +/- 8; P < 0.001; FEMg, 4. 1 +/-1; P < 0.001) were significantly different from those of patients with MesP-NS without TIF, and two of five variables (FECa, FEMg) were statistically different from those of patients with MesP-NS with TIF. In the severe category of FSGS (TIF, 69% +/-19%), all FE solutes were statistically different from the other groups (FENa, 4.8 +/- 3; FECa, 2 +/- 1; FEPO4, 47 +/- 24; FEUA, 37 +/- 18; FEMg, 12 +/- 6). Thus, the results imply that (1) normal tubular transport reflects an underlying intact tubulointerstitial structure, whereas tubular dysfunction indicates an underlying tubulointerstitial disease, and (2) FEMg is the most sensitive index to detect an early abnormality of tubular structure and function.

Staphylococcus aureus nasal carriage in children receiving long-term peritoneal dialysis.

The frequency of Staphylococcus aureus (SA) nasal carriage and the impact of antibiotic therapy remain undefined in children receiving long-term peritoneal dialysis (PD). We obtained a nasal culture for SA every 4-12 weeks in 21 children (mean age 7.03 +/- 5.8 years) receiving PD from January 1992 to August 1996 (total of 35.3 patient-years). In each case, SA nasal carriage (NSA+) was treated with intranasal mupirocin for 7 days. NSA+ was detected in 13 patients (61.9%) who received dialysis for 28.9 patient-years. Eight (61.5%) of 13 patients became NSA+ during the initial 3 months of dialysis. Seven (53.8%) of the NSA+ patients had 11 exit-site infections (ESI) and one episode of peritonitis (0.42 total infections/patient-year) due to SA. The 8 patients without SA nasal carriage (NSA-) received dialysis for 6.4 patient-years. None of the NSA-patients had an ESI or peritonitis with SA. Finally, the incidence of non-SA infections in the NSA+ and NSA- groups was not different (0.62 vs 0.31 total infections/patient-year, p > 0.05). In conclusion, there appears to be an association between SA nasal carriage and SA ESI in children on PD. The risk of SA peritonitis in NSA+ patients treated with mupirocin may be minimal. The risk of SA nasal carriage may increase with time on dialysis.

Renal perfusion and disease progression.

The pathogenetic concept of renal hyperperfusion and hyperfiltration in inducing glomerular pathology and disease progression documented in the renal ablation model in experimental animals to mimic renal disease with reduced nephron mass has recently been challenged. In contrast to the above, the intrarenal hemodynamic study in a variety of chronic glomerulonephropathies reveals a unique characteristic of renal hypoperfusion rather than hyperperfusion. This is associated with an elevated renal arteriolar resistance and reductions in renal plasma flow and peritubular capillary blood flow. The magnitude of reduction in peritubular capillary blood flow is inversely proportional to the degree of tubulointerstitial disease and tubular dysfunction. A progressive reduction in the vascular space due to nonvascular expansion with disease progression supports the concept of hypoperfusion of a whole kidney as well as a single nephron. In accordance with the renal ablation model and early diabetes mellitus, a similar hypoperfusion pattern is also subsequently observed in the chronic stage of renal ablation model in animals and late diabetic nephropathy. The disparity between the hyperperfusion and hypoperfusion in inducing renal disease progression can be enlightened by the Noble Truth of Lord Buddha stating "The Middle Tract is The Balance of Nature". Further support of this conceptual view of renal hypoperfusion as a determinant of tubulointerstitial disease and disease progression is in accordance with the therapeutic benefit with an enhanced-renal-perfusion formula per se in a variety of chronic glomerulonephropathies.

Chronic renal failure in Thai children: etiology, cost, and outcome.

We studied the epidemiology, cost and outcome of chronic renal failure (CRF) in Thai children by sending questionnaires to all university hospitals, all government general service hospitals and all pediatric nephrologists in the country. A total of 238 cases (107 from 8 university hospitals and 131 from 70 government general service hospitals) were diagnosed from 1996 to 1998. Mean age of the patients was 8.3 +/- 4.9 yr, male to female ratio was 1.4:1. Congenital KUB anomalies (obstructive uropathy and hypo/dysplasia) were the main causes of CRF in these patients, especially in the under five age group. Only a small number of patients received renal replacement therapy (chronic dialysis and kidney transplant) and the mortality rate was 18.7 per cent in university hospitals. Renal transplantation was performed in only 5 patients in 2 pediatric units and another 2 patients in adult renal units. The outcome of renal transplantation in this small group of patients was very satisfactory. The cost of CRF treatment in children was comparable to adults. The main problems in the management of CRF in Thai children included the lack of experienced personnel, lack of equipment and funding. We conclude that in order to improve the care of CRF in Thai children, a training program for health personnel and budget allocation should be established.

Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators.

Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.

Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients.

BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

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 tubulo-interstitial fibrosis and thereby supports the concept of renal perfusion as a crucial determinant of nephronal structure.