Urinary phosphate-containing nanoparticle contributes to inflammation and kidney injury in a salt-sensitive hypertension rat model.

Although disturbed phosphate metabolism frequently accompanies chronic kidney disease (CKD), its causal role in CKD progression remains unclear. It is also not fully understood how excess salt induces organ damage. We here show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. In Dahl salt-sensitive rats, salt loading resulted in a significant increase in urinary phosphate excretion without altering serum phosphate levels. An intestinal phosphate binder sucroferric oxyhydroxide attenuated renal inflammation and proteinuria in this model, along with the suppression of phosphaturia. Using cultured proximal tubule cells, we confirmed direct pathogenic roles of phosphate-containing nanoparticles in renal tubules. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with altered phosphate metabolism. These data demonstrate that increased phosphate excretion promotes renal inflammation in salt-sensitive hypertension and suggest a role of disturbed phosphate metabolism in the pathophysiology of hypertensive kidney disease and high salt-induced kidney injury.

Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis.

Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-κB (NF-κB)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-κB/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-κB/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis.

[Nephrotic proteinuria in hypertensive nephrosclerosis: clinical and evolution characteristics]. / Proteinuria de tipo nefrótico en la nefroangioesclerosis hipertensiva: características clínicas y evolutivas.

BACKGROUND AND OBJECTIVE: Nephrotic range proteinuria can occur in patients with biopsy proven hypertensive nephrosclerosis (HN). We analysed the differential clinical and evolution characteristics of these patients compared with other glomerular diseases. MATERIAL AND METHOD: This is a case-control descriptive analysis obtained from the renal pathology registry of our hospital. Clinical features, treatment and evolution of these patients (cases) were compared with nephrotic patients with other glomerular diseases (controls). RESULTS: Five point one percent of biopsies with HN diagnosis. Case/control characteristics were: proteinuria 4.7 [3-11.4] versus 5.5 [3-28.1] g/24h/1.73m(2) (P=NS). Normal albumin compared with controls (39.5 [6.4] versus 29.4 [10] g/dL; P=.001), significant oedemas only in 10 versus 63% of controls. HN were older (58.8 [12.6] versus 45.5 [19.6] years), had longer hypertension duration before renal biopsy and more previous cardiovascular events (39 versus 16%). Mean blood pressure was higher (166/90 versus 133/75mmHg; P=.01) and had worse renal outcome. CONCLUSIONS: HN must be included in the differential diagnosis of nephrotic range proteinuria in hypertensive patients. The absence of oedema and normal serum albumin are distinctive clinical characteristics that can help in decision-making before performing a renal biopsy.

Altered urinary excretion of aquaporin 2 in IgA nephropathy.

OBJECTIVE: The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indirectly, via RAS activation. Our aim is to explore the intrarenal activity of AVP, its relationship with RAS activity, as well as its modulation by therapies in IgAN. DESIGN: In this observational study, we measured plasma copeptin, a surrogate marker of AVP, the urine excretion of aquaporin 2 (AQP2), a protein reflecting renal AVP action, and angiotensinogen (AGT), a parameter of renal RAS activation, and their relationship with renal function in 44 IgAN patients at the time of renal biopsy, without any drug therapy, and after 6-month treatment with ACEi or steroid+ACEi. Twenty-one patients with other CKD and 40 healthy subjects were recruited as controls. METHODS: ELISAs were used to measure all variables of interest. RESULTS: At baseline, IgAN patients showed higher urinary levels of AQP2, compared with controls and patients with other CKD. Urinary AQP2 and AGT levels strongly correlated with the presence of arterial hypertension. Steroids+ACEi caused the decrease of all the variables examined. The fall of urinary AQP2 and AGT following drug treatments was associated with the decrease of daily proteinuria. CONCLUSION: Our findings would support the involvement of AVP-AQP2 axis, interacting with the RAS, in the progression of IgAN and candidate AQP2 as a possible novel marker of the disease.

A comparative study of three kidney biomarker tests in autosomal-dominant polycystic kidney disease.

BACKGROUND: The relationship between the progress of tubular damage and renal insufficiency in autosomal-dominant polycystic kidney disease (ADPKD) is a subject of doubtless interest, and is the object of this present work. METHODS: A total of 92 adult ADPKD patients of both genders were studied, none of which presented end-stage renal disease (ESRD), and classified according to an ultrasound score based on kidney size and number of cysts. Urinary albumin and beta-N-acetylhexosaminidase (Hex) and its isoenzymes were determined, together with serum glutathione peroxidase, cystatin C, creatinine, and urea. RESULTS: A frequent elevation of the urinary Hex was found and an alteration of its isoenzymatic profile, with 31% of the normotensive patients with normoalbuminuria already presenting an increased proportion of Hex B isoenzyme. Keeping age constant, a partial significant correlation was found between the ultrasound score and the proportion of Hex B (r = 0.352, P < 0.05), but not with albuminuria or cystatin C. In 42 patients the different biochemical variables were again determined after 1 year, finding that in the 13 normotensive patients with normoalbuminuria there had been a significant decrease in the concentration of cystatin C (P < 0.05), and a significant increase in the urinary excretion of albumin and Hex B isoenzyme (P < 0.05). By the other hand, in the other 29 patients with micro- or macroalbuminuria and hypertension, no significant differences were found. CONCLUSION: The results point toward an important participation of tubular damage in the pathogenesis of this disease. It may also be suggested that in normotensive and normoalbuminuric ADPKD patients, a gradual increase of glomerular filtration would be produced. After the start of hypertension and microalbuminuria, the glomerular filtration rate (GFR) would decrease progressively, although more slowly.

Sex differences in renal injury and nitric oxide production in renal wrap hypertension.

To investigate the faster rate of renal disease progression in men compared with women, we addressed the following questions in the renal wrap (RW) model of hypertension: 1) Do sex differences exist in RW-induced renal injury, which are independent of sex differences in blood pressure? 2) Do sex differences in nitric oxide (NO) production exist in RW hypertension? Male (M) and female (F) rats underwent sham-operated (M-Sham, n = 7; F-Sham, n = 10) or RW (M-RW, n = 13; F-RW, n = 14) surgery for 9 wk. Markers of renal injury, including the glomerulosclerosis index (F-RW, 0.70 +/- 0.1 vs. M-RW, 2.2 +/- 0.6; P < 0.05), mean glomerular volume (F-RW, 1.05 +/- 0.050 x 10(6) vs. M-RW, 1.78 +/- 0.15 x 10(6) microm(3); P < 0.001), and proteinuria (F-RW, 68.7 +/- 15 vs. M-RW, 124 +/- 7.7 mg/day; P < 0.001) were greater in RW males compared with RW females. Endothelial NO synthase protein expression was elevated in the renal cortex (3.2-fold) and medulla (2.2-fold) 9 wk after RW in males, whereas no differences were observed in females. Neuronal NO synthase protein expression was unchanged in the renal cortex in males and in both the renal cortex and medulla in females, whereas in the male medulla, neuronal NOS was decreased by 57%. These data suggest the degree of renal injury is greater in male compared with female rats in RW hypertension despite similar degrees of hypertension and renal function and may involve sex differences in renal NO metabolism.

Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.

Albuminuria in nondiabetic relatives of IDDM patients with and without diabetic nephropathy.

BACKGROUND: In non-insulin-dependent diabetes mellitus (NIDDM), there is a clustering of an elevated urinary albumin excretion rate (U-AER) in nondiabetic relatives of albuminuric patients. Whether this is also the case in insulin-dependent diabetes mellitus (IDDM) is unknown. METHODS: Overnight U-AER was measured in 186 nondiabetic first-degree relatives of 80 IDDM patients with diabetic nephropathy (U-AER > 200 microg/min or 300 mg/24 hours; DN+) and in 52 relatives of 25 IDDM patients without nephropathy (U-AER < 20 microg/min; DN-). The two groups of relatives were comparable regarding gender distribution, age, obesity, blood pressure, prevalence of antihypertensive therapy, and smoking habits. RESULTS: No difference was found in overnight U-AER between relatives of patients with DN+ and DN- [median (range), 3.4 (0.1 to 372) vs. 4.0 (0.2 to 62) microg/min, respectively, P = NS]. The proportion of relatives with a U-AER = 10 microg/min was 12% in DN+ compared with 8% in DN- (P = NS). Among relatives of DN+, those with antihypertensive treatment (AHT+) had higher U-AER compared with those without [AHT+ vs. AHT-, 5.0 (0.5 to 372) vs. 3.4 (0.1 to 26.5) microg/min, P < 0.01], a phenomenon that was not seen among relatives of DN-[AHT + vs. AHT-, 3.6 (2.1 to 24.3) vs. 4.0 (0. 2 to 61.5) microg/min, P = NS]. However, this analysis was impaired by the small number of relatives of DN- with hypertension (N = 7). CONCLUSIONS: In IDDM, we found no clustering of elevated U-AER in nondiabetic relatives of patients with nephropathy. This is different from what has been reported in NIDDM, and suggests heterogeneity in the genesis of albuminuria in diabetes.

Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study.

BACKGROUND: Microalbuminuria is a risk factor for cardiovascular disease, but the underlying pathomechanisms are still poorly understood. A relationship between C-reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic disease has been reported recently. METHODS: We hypothesized that microalbuminuria might be associated with chronic inflammation and investigated the relationship of urinary albumin excretion, as assessed from the albumin-to-creatinine ratio (ACR), in an untimed morning urine specimen, and two inflammatory markers (CRP and fibrinogen) in the large, triethnic population of the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects with macroalbuminuria, 1481 subjects were studied. RESULTS: Both inflammatory markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for fibrinogen, both P = 0.0001), an association that remained significant after adjustment for demographic variables, diabetic status, smoking, and use of angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N = 1219) subjects (5.37 +/- 0.47 vs. 3.80 +/- 0.15 mg/L and 295.7 +/- 4. 0 vs. 278.2 +/- 1.6 mg/dL, both P < 0.0001). The associations were consistent among nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model, fibrinogen was independently associated with microalbuminuria (P = 0.047), along with hypertension, female gender, waist circumference, and fasting blood glucose, while CRP was not independently related to microalbuminuria in this model (P = 0.26). CONCLUSION: We have shown an association of CRP and fibrinogen with urinary albumin excretion in the microalbuminuric range in type 2 diabetic and nondiabetic individuals. Chronic inflammation therefore emerges as a potential mediator between microalbuminuria and macrovascular disease.

[Urinary fibronectin as an indicator of kidney fibrosis in nephritis]. / Fibronektin mochi kak pokazatel' protsessov fibrozirovaniia v pochke pri nefrite.

AIM: To investigate clinicomorphological relationships between elevated urinary excretion of fibronectin (FN) and development of fibrosis in the kidney in patients with lupus nephritis (LN) and chronic glomerulonephritis (CGN). MATERIALS AND METHODS: Urinary FN excretion was measured at radial immunodiffusion in 54 LN patients. Of them, 15 patients had inactive LN, 39 patients had active LN varying in clinical forms. Urinary FN was also measured by passive hemagglutination in 36 CGN patients (11 inactive CGN and 25 active CGN cases). Biopsy specimens were obtained from 49 patients with active nephritis (43 with CGN and 6 with LN). FN deposits were studied immunohistochemically and morphometrically with determination of relative fibrosis area. RESULTS: Urinary FN excretion in patients with nephritis was higher than in healthy controls. In active CGN and LN the levels of FN were significantly higher than in inactive CGN and LN. The highest FN urinary concentrations were registered in patients with severe CGN and LN, especially in the presence of renal failure and arterial hypertension. Among them, the highest individual values were observed in patients with rapidly progressive nephritis. No positive correlations were found between the degree of the urinary FN excretion increment and degree of proteinuria. This suggests local-renal origin of most urinary FN. Morphologically, FN deposits were revealed in 73% of the biopsies. In most of the patients with severe nephritis both in CGN and LN there was a diffuse distribution of FN in the glomerules and interstitium. A correlation with a morphological nephritis type was absent, but existed between FN presence in the renal biopsies and relative area of interstitium (fibrosis). CONCLUSION: FN excreted in high amounts with urine in nephritis originates from the kidneys and reflects severity of fibrogenesis in the kidney.

Serum homocysteine level and protein intake are related to risk of microalbuminuria: the Hoorn Study.

BACKGROUND: Microalbuminuria (MA) is a strong predictor of cardiovascular disease, but its causes are incompletely understood. Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease independent of established risk factors. It is not known whether hyperhomocysteinemia is associated with MA, and thus could be a possible cause of microalbuminuria. METHODS: We studied an age-, sex- and glucose-tolerance-stratified random sample of a 50- to 75-year old general Caucasian population (N = 680). The urinary albumin-to-creatinine ratio (ACR) was measured in an early morning spot urine sample. MA was defined as an ACR > 3.0 mg/mmol. RESULTS: The prevalence of MA was 4.3% (13 of 304) in subjects with normal glucose tolerance, 9.2% (17 of 185) in impaired glucose tolerance and 18.3% (30 of 164) in non-insulin-dependent diabetes mellitus (NIDDM); it was 3.7% (15 of 402) in subjects without hypertension and 17.9% (45 of 251) in those with hypertension. After adjusting for age, sex, glucose tolerance category, hypertension, dyslipidemia and smoking, the odds ratio [OR; 95% confidence interval (95%CI)] for MA per 5 mumol/liter total homocysteine increment was 1.33 (1.08 to 1.63). Additional adjustment for HbA1c, waist-hip ratio, protein intake and serum creatinine did not attenuate the association between MA and total homocysteine. A 0.1 g/kg.day increment of protein intake was also associated with an increased risk for MA after adjustment for age, sex, classical risk factors and serum total homocysteine [OR (95% CI); 1.20 (1.08 to 1.32)]. CONCLUSION: Both hyperhomocysteinemia and protein intake are related to microalbuminuria independent of NIDDM and hypertension. Hyperhomocysteinemia may partly explain the link between MA and increased risk of cardiovascular disease.

Increased urinary catecholamines in a hypertensive child with renal artery stenosis.

We report a hypertensive child with renal artery stenosis who exhibited increased urinary excretion of norepinephrine (NE) and normetanephrine (NMN), while vanillylmandelic acid (VMA) excretion was within the normal range. The NMN values prompted us to investigate the patient for pheochromocytoma; for this purpose, NE was determined by plasma catecholamine assays in venous samples obtained by catheterization. The moderately increased NE levels could not be localized to any particular sampling site. Arteriography demonstrated right renal artery abnormalities. Following right nephrectomy with preservation of the right adrenal gland, arterial blood pressure returned to normal. The cause of increased NMN excretion without a concomitant rise in VMA during hypertension is discussed.

Beta-2 microglobulinuria and long-term outcome following curative surgery for primary hyperparathyroidism.

Twentyseven patients admitted for surgery for primary hyperparathyroidism were studied preoperatively. Fifteen were normotensive and 12 were either hypertensive, diastolic blood pressure > 95 mmHg or had a raised serum creatinine measuring 109.7 (55-171) mumol/l. The beta 2 microglobulin (beta 2M) urinary excretion was measured on all patients. The beta 2M levels were raised in all patients preoperatively even in those patients who had normal values for conventional renal function tests. Following curative surgery the values are returned to the normal range. The patients were followed up for a mean of 4.2 (2.8-5.6) years. Six patients who were initially normotensive subsequently developed hypertension and the initial beta 2M ratio was significantly higher 386 (122-680) micrograms/l compared to those who remained normotensive 186 (95-340) micrograms/l (p < 0.05). Even higher preoperative beta 2M excretion was found in the initial hypertensive group 505 (87-1160) micrograms/l compared to those who later developed hypertension 386 (122-680) micrograms/l, p < 0.001. This preliminary study suggests that preoperative beta 2M urinary excretion may be of value in identifying those patients who will subsequently develop hypertension, an identified long term cause of death in patients operated on for primary hyperparathyroidism. Further studies are indicated.

Role of cadmium in hypertensive patients with renal parenchymal disease.

In our study we investigated 36 out-patients with renal disease; 22 of them were hypertensive. In all patients proteinuria was present (4.30 +/- 0.82 g protein/d) and renal involvement has been proved by renal biopsy. Blood cadmium in nonsmokers was significantly (P less than .05) lower than in smokers. Patients with renal hypertension showed a significantly higher (P less than .05) urine cadmium excretion/d (1.60 +/- 0.23 micrograms/d) compared to normotensives with a disease of the kidney (1.14 +/- 0.38 micrograms/d). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction.

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.

A case of renovascular hypertension with high urinary noradrenaline excretion.

A case report of 32-year-old male with renovascular hypertension, suspected to be pheochromocytoma as a result of a tentative diagnosis, is given. The suspicion was based on the observation of high levels of urinary noradrenaline on several occasions with the sign of hyperreninemia. Reduction of the urinary noradrenaline levels by the administration of angiotensin converting enzyme inhibitor (SQ-14225) suggested that the high urinary noradrenaline probably resulted from hyperreninemia which reflected high plasma levels of angiotensin II. Radioisotope renography and intravenous urography strongly suggested a reduction of the right renal blood flow, and the final diagnosis of renovascular hypertension was obtained on the basis of renal arteriography. On the other hand, the possibility of a catecholamine releasing tumor was carefully excluded by angiography before undertaking surgical treatment. The affected kidney was transplanted autogenously into the abdominal cavity. The successful operation led to a decrease in plasma renin activity, blood pressure and urinary noradrenaline excretion. In the present case, we were thus unable to define at first whether the primary genesis of hypertension was related to the hyperactivity of the renin-angiotensin system caused by renovascular stenosis or a noradrenaline releasing tumor.

Hypertension in polycystic kidney disease without renal failure.

Hypertension occurring in patients with adult polycystic kidney disease (PKD) without substantially decreased glomerular filtration rate (GFRs) has not been sufficiently evaluated. Seven patients with bilateral PKD and serum creatinine clearances greater than 70 ml/min were studied to examine the roles of sodium retention and the renin-angiotensin system in their hypertension. These individuals demonstrated evidence of volume expansion and sodium-dependent hypertension. However, the renin-angiotensin system was not consistently depressed as a consequence, and two of the seven had significantly increased plasma renin activity values. It seems that patients with PKD who had normal GFRs retain rather than waste sodium and may become hypertensive. The contribution of the renin-angiotensin system is variable and seems to be a function of such factors as symmetry of the cystic involvement and the degree of intravascular volume expansion.

[Urine specific gravity and osmolarity in hypertension patients with dehydration]. / Spetsifichno teglo i osmolalnost na urinata pri khipertonichno bolni v usloviia na dekhidratatsiia

Results are reported from the comparative investigations of kidney concentration function by urine specific gravity and its osmolatity of 58 patients with arterial hypertension. Significant differences were found in more of the half of the patients. On the base of certain theoretical prerequisites and possibilities of technical errors was concluded that the determination of the maximal urine osmolality is a more reliable and more accurate index for the actual renal concentration ability. Urine specific gravity can be used in the everyday clinical practice due to the more convenient and easier determination. Urine osmolality must be used predominantly in scientific-clinical studies.

Urinary kallikrein excretion and sodium metabolism in hypertensive patients.

Urinary kallikrein excretion was measured in 21 healthy subjects and 44 patients with various types of hypertension. The kallikrein activity was determined by the method of esterolytic assay. The excretion rates in normal subjects were 112.9 +/- 11.1 (S.E.) EU/day. The kallikrein excretion was decreased in patients with essential hypertension, the mean estimated values were 75.2 +/- 10.0 EU/day. In this disease, however, an enhancement of urinary kallikrein was observed after sodium depletion. An obvious increase in kallikrein excretion was found in the primary aldosteronism. In primary aldosteronism and renovascular hypertension, one of the secondary aldosteronisms, there was a good correlation between the urinary kallikrein output and the urinary sodium excretion. The present data indicate that the renal kallikrein-kinin system, one of the renal antihypertensive factors, is suppressed in essential hypertension and is under the influence of mineralocorticoid levels.

Hypertension due to renal artery stenosis in transplanted kidneys.

Hypertension appeared to be related to stenosis of the hypogastricrenal artery system in 5 patients among 153 recipients of renal allografts. Renin assay and arteriography were crucial in the comprehensive evaluation of patients whose hypertension was not clearly related to rejection or excessive sodium intake. Hypereninemia was persistent in 4 of the 5 patients. Stenoses of the transplant renal arteries in three patients were caused by extensive intimal plaque formation. In one patient, periarterial fibrosis caused reduction of flow; 180 degrees torsion of the anastomosis resulted in stenosis in the fifth patient. Surgical correction is difficult and may be facilitated by a transabdominal approach. Vein bypass is probably preferable to patch angioplasty for intimal lesions. Following operation, hypertension was ameliorated and function improved in all patients. Rejection, which has been suggested as one of the causes of intimal plaque formation, ultimately led to the loss of the transplant in one patient. Function is normal in two patients; two patients have evidence of chronic rejection. No effort should be spared to evaluate this special group of patients whose transplant function can predictably be prolonged by decisive surgical management.