Autosomal dominant polycystic kidney disease (ADPKD) is one of the major causative diseases leading to renal failure and dialysis treatment. Although the genetic study on the disease has been progressed so far, the initial trigger for cyst formation and several factors enhancing the progression of ADPKD remain to be clarified. Using an animal model of ADPKD, induced by 2-amino-4, 5-diphenylthiazole hydrochrolide (DPT), we examined the early events in cystogenesis. Especially the role of tubular obstruction in the model in triggering off tubular dilatation was investigated by means of renal micropuncture and tubular microperfusion technipues. Light and electron microscopic studies demonstrated epithelial hyperplasia along collecting ducts after 2 weeks of DPT feeding. In addition, some collecting ducts revealed partial obstruction with hyperplastic cells. Cystic change became prominent over 8 weeks of the treatment. Then micropuncture and microperfusion experiments were performed to measure intratubular pressure in the rats fed DPT for 2-5 weeks (PKD rats) and pair-fed control Sprague-Dawley rats (control rats). Free flow pressure in proximal segments of PKD rats (21.5±1.0mmHg) was not significantly elevated, as compared with that in control rats (21.3±1.OmmHg). During the stepwise increments in proximal tubular flow rate, proximal tubular pressure in PKD rats significantly increased especially at higher flow rate, 41.0±3.6 mmHg in PKD rats and 19.4±3.1mmHg in control rats (P<O. 01) at 40nl/min. On the other hand, the transit time of loop of Henle was longer in PKD rats (38. 9±2. 4sec) than in control rats (24. 9±0. 6sec, P<0. 01). These results suggest that cyst formation in PKD rats could be preceded by the elevation of tubular resistance, which might be explained by the partial obstruction of collecting ducts. Moreover, these tubular obstruction in the distal segments might be the trigger for the cyst formation in this model.

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The influence of glucose concentration on proliferation and collagen production was studied in rat cultured mesangial cells. The cells at passage 6-8 were cultured in 10% FCS/DMEM with different glucose concentrations (5, 15 or 25 mM). (³H) thymidine uptake was significantly suppressed in 25 mM glucose condition in the presence or absence of FCS. Immunocytochemistry revealed a dramatic increase in intracellular staining for collagen I, III and N in 25 mM glucose condition. Analysis of soluble extracellular matrix production using ELISA also showed increased concentration of collagen I, III and IV in the supernatant of mesangial cells grown in 25 mM glucose. The message for collagen I, III and IV increased and decreased rapidly within 24 h after refeeding, making a first peak of message level. After 24h mRNA for collagen I, III and IVincreased again in 25 mM glucose media, whereas the message remained depressed in 5 mM glucose media. These results obtained from in vitro studies suggest that high blood glucose per se may play an important role in increased extracellular matrix in diabetic glomerulosclerosis.

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The effects of angiotensin-converting enzyme (ACE) inhibitors, rampipril, captopril and enalapril, on the renal circulation and function were examined in normotensive dogs, in relation to the renin-angiotensin-aldosterone (R-A-A) and kallikrein-kinin (K-K) systems and prostaglandins (PGs). These inhibitors markedly decreased renal vascular resistance (RVR) in parallel with a reduction in systemic blood pressure, and increased renal blood flow (RBF). Captopril exerted its effects rapidly, but its disappearance was also rapid. The onset of ramipril's effects was slightly delayed, but its antihypertensive and RVR-decreasing effects were fairly prolonged. Ramipril showed more potent and longer-lasting RBF-increasing effect and induced marked Na diuresis. Enalapril had no diuretic effect, and captopril's effect was only temporary. Plasma renin activity was increased similarly by the three inhibitors, but only ramipril significantly decreased plasma aldosterone concentration. This aldosterone secretion inhibition by ramipril may be partly involved in the diuretic effect. Involvement of the K-K system and PGs in ramipril's effects on the dog kidney was examined. When systemic PG biosynthesis was inhibited by indomethacin pretreatment, ramiprill-induced increases in RBF and urine volume were inhibited about 50%. Inhibition of the K-K system by aprotinin pretreatment resulted in marked inhibition of urine volume increase, but scarecely affected RBF increase. These results indicate that ramipril produces the most potent effect on the renal circulation and function of the dog among the three ACE inhibitors and that its diuretic action is mostly due to kinins and kinin-induced PGs in the kidney and the RBF increase, due to the R-A-A system and PGs.

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We are carried out to determine the detection of glycosylated protein of renal tissues using nitroblue tetrazorium (NBT) reaction in streptozotosin (STZ)-induced diabetic rats. The levels of glomerular non-enzymatic glycosylation were measured by thiobarbituric acid (TBA) method. There was no significant difference in the intensity of NBT in renal tissues between the 4-week diabetic rats and the same age control rats. The intensity of NBT in the glomerular mesangial areas and capillary walls was marked in 12-week diabetic rats. The staining of NBT was also observed in the tubular epithelial cells in 4-and 12-week diabetic rats. The levels of glomerular non-enzymatic glycosylated protein in 4-or 12-week diabetic rats were significantly greater than those in the same age control rats. It appears that the non-enzymatic glycosylation of renal tissues increased in the early stage of diabetic nephropathy, i. e. 4- or 12-week diabetic rats. It is concluded that the non-enzymatic glycosylation may play an inportant role in the initiation of renal injuries in diabetic nephropathy.

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Glomerular filtration rate has been found to be elevated in the early stage of insulindependent diabetes mellitus and has been proposed to play a pathogenetic role in the development of diabetic nephropathy. However, the reports about the change in renal plasma flow (RPF) among diabetic supjects were inconsistent, suggesting that the presence of hyperglycemia may in some way interfere the procedures of RPF measurement. Recently, it has been reported that the glucose in the urine may react with p-aminohippurate (PAR), a widely used marker for RPF measurement, and influence the chemical measurement of PAH, misleading the result of RPF value. In fact, we obtained the decrease of PAH value in urine samples obtained from diabetic subjects during the storage for one week in flozen condition. In order to clarify the factors which may influence the glucose-PAH reaction, we have conducted various in vitro studies. The decrease of PAH values was dose-dependent to urine glucose. The pH of the test solution or urine was also found to greatly influence the result of PAH measurement when glucose was present. The analysis of glucose-PAH reactants by HPLC suggested that the aminoresidue of PAH might be reacted with glucose, producing the glycation product (Schiff base). The rate of glycation of PAH was time- and pH-dependent. However, when the reaction time was prolonged at the last step of PAH measurement after the addition of the acid solution, the decrease of PAH value was gradually corrected reaching to the theoretical value in 7 hours. From these results it might be recommended that on the measurement of RPF using PAH method urine samples have to be treated with acid prior to the measurement or the last reaction of PAH measurement has to be prolonged at least for 7 hours.

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From August 1989 through September 1991 we performed percutaneous nephrostomy under ultrasonic guidance in 26 kidneys of 25 patients. We also indwelled double pigtail ureteral stents by endoscopy in 14 kidneys of 13 patients. No patients died because of renal failure. The survival was dependent on progression of primary disease and performance status. Neither significant nor lifethreatening complications were encountered. The difference in the improvement of renal function between nephrostomy group and stent group was not statistically significant. Although the indwelling ureteral stent method requires no external drainage bag, this method has certain drawback such as occasional obstruction of stent. Especially in poor risk patients, percutaneous nephrostomy technique seems to be better than placement of double pigtail ureteral stent in the treatment of postrenal failure secondary to malignancies.

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Overloaded sodium (Na) induces the expansion of extracellular volume in case with severe renal insufficiency. Accordingly, in patients undergoing CAPD, the Na balance viatrans-peritoneum is the critical determinant of fluid state. This study was performed to clarify the trans-peritoneal Na kinetics in patients using standard dialysate (Na:l32mEq/1, 2-1), and to explore the clinical effects of lower Na concentration solution. Peritoneal dialysis effluent obtained from 87 patients was analysed [1.5%dextrose dialysate (D): 33 bags, 2.5%D: 54 bags]. In terms of net-Na removal, no significant relation was found with serum Na level. Whereas, a significant positive relation was found with ultra filtration (UF) volume (p<0. 01). Net-Na removal was 10.0±3.3mEq in 1.5%D and 30.2±1 . 8 mEq in 2.5%D (mean±SEM). On the other hand, ultra low sodium concentration dialysate (ULNaD, Na level: 98mEq/l, Osm: 340mOsm/ 1, 2 4) was effectively used for the purpose of increasing Na removal. Net-Na removal was 78.1±5.6mEq after 4-hr dwelling (n=18) . ULNaD was applied to ten patients who showed signs of overhydration, using once a day consequtively instead of standard one. After 9 days (mean) in this regimen, signs of overhydration were disappeared. Significant reductions in their body weight and fall in blood pressure were found compared to the periods before commencement of ULNaD, showing remarkable increase in Na removal (p<0.01, respectively). No significant changes were found in serum Na level or OF volume. These results indicate that in the case using standard dialysate, Na removal is mainly depending on the OF volume, suggesting that sufficient Na removal is not expected unless OF volume increases. On the other hand, ULNaD yields Na removal by the concentration gradient force, which does not require the increment of OF volume. Clinically, ULNaD can be effectively used for the correction of fluid excess state seen in CAPD.

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Ultrafiltration volume (UFV) in peritoneal dialysis is expressed as the difference between net transcapillary ultrafiltration (TCUF) and lymphatic absorption (LA) in peritoneal cavity. An increase in LA results in a decrease in UFV. Endogenous hormones may modulate peritoneal membrane permeability and LA. This study was conducted to assess the effect of angiotensin II(AII) on peritoneal permeability and LA in rat. Rats (BW, approximately 300g) with normal renal function were dialyzed for 4 hours using 30m1 of hypertonic dialysate (dextrose concentration: 3.86%). AII was added in dialysate at the concentration of 10^-9-10^-2 mol/30ml. Peritoneal membrane permeability and UFV were studied by clearance of urea N and inorganic phosphate, albumin excretion, glucose absorption and LA. LA was calculated by the concentration change of dextran 70 in dialysate. AII decreased UFV from 15. 7±2. 8ml/4hr(control) to 5.7±1.5(VII10^-4 mol/dwell). LA was increased in a dose dependent fashion (ED₅₀: 0.25×10^-6mol) with no change in TCUF and clearances of urea N and inorganic phosphate. Ten types of AII analogue were used to investigate the site of action for LA in 8 amino acids of AII. [β-Asp¹], [Val⁵], [Ile³, Val⁵] and [Sar¹] AII showed agonistic action against LA. [Sar¹, Thr⁸], [Sar¹, Ile⁸], [Sar¹, Leu⁸], [Sar¹, Ala⁸], [Sar¹, Val⁵, Ala⁸] and [Sar¹, Gly⁸] AII had no effect on LA, which found the importance of the 8th amino acid of AII for LA. These actions of AII analogue against LA were similar to those for vascular smooth muscle. An increase in LA with AII was reduced by 40% in the rat with a sealing diaphragm. In conclusion, peritoneal administration of AII decreased UFV by an enhancement of LA. Subdiaphragmatic lymph system played an important role for this increase in LA.

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A 64-yr-old man presented with diabetes mellitus, proteinuria, hypertension and moderate renal dysfunction. Renal biopsy revealed diabetic glomerulosclerosis (diffuse lesion), IgA nephropathy and membranous nepphropathy (stage 2). Both mesangial IgA and subepithelial IgG deposits were demonstrated by immunofluorescence and immunoelectron microscopy, Electron microscopic studies by immunogold method showed localization of IgA (diameter l5nm gold particles) within mesangial dense deposits and IgG (diameter l5nm gold particles) within subepithelial dense deposits. Overlapping IgA and membranous nephropathy was revealed in the same diabetic glomeruli with functional and biochemical alternations.

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A male aged 58 was admitted to our hospital because of proteinuria, hematuria and bilateral pretibial edema. Laboratory tests showed normocytic, normochromic anemia and moderately impaired renal function. Antinuclear antibodies were negative. Neither M-protein nor Bence-Jones protein were detected. Light microscopic study on the biopsied renal specimen indicated a moderate mesangial proliferation accompanying with the deposition of PAS-positive and Congo red-negative materials in the subendothelial area. C3 accumulated segmentally along the capillary walls, which was clarified by immunofluorescence microscopy. Staining for IgG, IgA, IgM and light chains were negative. Electron microscopy demonstrated the deposition of microtubules in the mesangial, subepithelial and subendothelial areas. The diameter of these microtubules ranged from 40 to 80 nm. Such type of the microtubules have been reported to exist in the glomeruli in the patients with systemic diseases such as amyloidosis, systemic lupus erythematosus, cryoglobulinemia and light chain disease. In our patient, however, any clinical or serological findings sugges tive of these systemic diseases were not obtained. On the other hand previous report pointed out that microtubules deposited in the glomeruli in the patients with immunotactoid glomerulopathy or other glomerulopathies. Our patient had the clinical features consistent with these glomerulopathies. However, no depositions of immunoglobulins were observed. This case is an atypical glomerulopathy accompanying with the glomerular microtubular deposits.

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The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2.5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense depositsin the subendthelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date.

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we describe a patient who presented frostbite in extremities in addition to characteristic symptoms, such as severe hypertension, sweating attacks, palpitations and headache. The patient was eventually diagnosed as having single extra-adrenal pheochromocytoma. The frostbite in extremities rapidly resolved after the removal of the tumor as well as other characteristic clinical symptoms. It is speculated that this frostbite might have been induced by severe continuous constriction of peripheral artery and loss of heat by frequent sweating attacks. Regarding cutaneous symptoms in this disease, pallor, acrocyanosis and cold extremities are commonly found. However, it seems that typical frostbite associated with pheochromocytoma has not been reported so far.

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A sixty nine-year-old woman was admitted to the hospital because of further examination of hypercalcemia. On July 1990, she complained of general fatigue and loss of appetite. She was pointed out to have hypercalcemia (15, lmg/dl), urolithiasis, and renal insufficiency. CT films of the chest showed swelling of the mediastinal lymhpnodes and CT of the abdomen nephrocalcinosis. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in the mediastinum. Levels of the parathyroid hormone was normal. Levels of the serum calcium (13, 7mg/dl), angiotensin converting enzyme (30.4IU/L) and 1.25 (OH)₂D (87PG/ml) were elevated. Giant cells were found in the biopy specimen of the lung. A significant relationship between the serum calcium and creatinine were observed (r=0.76, p<0 .02). Proximal fractional reabsorption of sodium showed to be supressed (47 .7%), and distal fractional reabsorption of sodium showed to be normal (88.4%). From these findings hypercalcemia and urolithiasis was suggested to result from sarcoidosis. The hypercalcemia and renal insufficiency improved with corticosteroid therapy.

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