Favorable course of collagenofibrotic glomerulopathy after kidney transplantation and questionnaire survey about the prognosis of collagenofibrotic glomerulopathy

Collagenofibrotic glomerulopathy is a recently recognized entity that is characterized by massive accumulation of collagen fibrils in the mesangial and subendothelial areas, and an elevated serum level of procollagen III peptide (PIIIP). We report the first case of a collagenofibrotic glomerulopathy patient who received a kidney transplantation. She received the kidney transplantation at the age of 18 years and the post-operative course was uneventful with good renal function on immunosuppression, which consisted of methylprednisolone, tacrolimus and basiliximab. Although urinary protein was negative, the serum level of PIIIP gradually elevated which suggests new collagen production in the graft. These findings indicate that the recipient had a systemic factor that stimulated collagen production. To investigate the prognosis of collagenofibrotic glomerulopathy, we carried out a questionnaire survey on 14 patients at 9 hospitals. None of these patients had received a kidney transplantation. However, 7 already had end-stage renal failure. Ten years after diagnosis, the renal survival rate was 49%. This rate is lower than cited in previous reports.     

Collagen Type III Glomerulopathies

The 2 rare disorders characterized by the pathological accumulation of collagen type III in glomeruli are discussed. These are collagenofibrotic glomerulopathy, also known as collagen type III glomerulopathy, and the nail-patella syndrome. Although there are similarities in abnormal morphology, with type III collagen in mesangium and/or capillary walls, there is no genetic or pathogenic link to them. Collagenofibrotic glomerulopathy presents either in childhood, often with a family history suggesting autosomal recessive inheritance, or in adults as a sporadic occurrence. Proteinuria is the typical manifestation, with progression to ESRD in approximately 10 years. Although there is markedly elevated serum precursor collagen type III protein in the circulation, the usual manner of diagnosis is with kidney biopsy, which discloses type III collagen in subendothelial aspects of capillary walls and often in the mesangial matrix. Glomerular involvement in the nail-patella syndrome invariably presents in a patient with an established diagnosis of this multisystem disorder with orthopedic and cutaneous manifestations. It is owing to mutations in the gene LMX1B. Although the lesion may be asymptomatic, it is usually manifested by proteinuria. Structural lesions are of collagen type III within glomerular basement membranes, different in distribution to collagenofibrotic glomerulopathy. The clinical course is variable.     

Clinical evaluation of cases with massive ascites accumulation after discontinuation of CAPD: an attempt to establish the concept of the pre-sclerosing encapsulating peritonitis(pre-SEP) state

Sclerosing encapsulating peritonitis(SEP) is a most serious complication of continuous ambulatory peritoneal dialysis(CAPD). Although the criteria of diagnosis and guidelines for therapy of SEP have been proposed by the Japanese SEP Study Group already, SEP is refractory to treatment when the disease process is complete. It is important to detect the latent phase of SEP(pre-SEP state) in order to treat patients at an early stage. We evaluated the characteristics of ascites in four patients with massive ascites accumulation after discontinuation of CAPD. Age and the duration of CAPD of the subjects were 53.3 +/- 9.7 years and 126.5 +/- 6.8 months, respectively. However, the patients were withdrawn from CAPD because of peritonitis or ultrafiltration failure. We also followed cytokines and parameters of collagen metabolism of ascites in two patients during adrenocorticosteroid therapy and conducted a histopathological evaluation of the peritoneum of an autopsy case who had died of pneumonia. Ascites seems to be exudative because of the high concentration of protein, cytokines and parameters of collagen metabolism such as interleukin-1 beta, interleukin-6, transforming growth factor-beta 1, procollagen 3 peptide, and type IV collagen 7S, the levels of which were 21.3 +/- 9.3 pg/ml, 8,153 +/- 7,327 pg/ml, 6.7 +/- 3.6 ng/ml, 89.3 +/- 67.8 U/ml, and 59.0 +/- 36.2 ng/ml, respectively. The histopathological findings of the peritoneum from the autopsy case showed dense fibrous tissue permeated with inflammatory infiltration and widespread infiltration of fibrin. These findings suggested that the peritoneum was inflamed when massive ascites accumulated. The amount of ascites and concentration of cytokines and parameters of collagen metabolism of ascites diminished during adrenocorticosteroid therapy. We concluded that massive and refractory accumulation of ascites appearing after the discontinuation of CAPD should be regarded as a sign of the pre-SEP state, and prophylactic treatment should be started at this stage of disease.     

Expression of heat shock proteins 47 and 70 in the peritoneum of patients on continuous ambulatory peritoneal dialysis

BACKGROUND: Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS: We determined the expression of HSP47 and HSP70 (nonspecific for collagen synthesis) by immunohistochemistry in peritoneal tissues of patients on CAPD. The tissue for collagen III, alpha-smooth muscle actin (alpha-SMA), and CD68 (a marker for macrophages) were also stained. Thirty-two peritoneal samples were divided into three groups (group A1, 11 patients who had no ultrafiltration loss; group A2, 9 patients who had ultrafiltration loss; and group B, 12 specimens who had end-stage renal disease prior to induction of CAPD. RESULTS: In group B, staining for HSP47, HSP70, and collagen III in peritoneal tissues was faint, and only a few cells were positive for alpha-SMA and CD68. In contrast, HSP47, HSP70, and collagen III were expressed in areas of thickened connective tissues in fibrotic peritoneal specimens of CAPD patients. The expression level of HSP47, HSP70, collagen III, and alpha-SMA and the number of CD68-positive cells in group A2 were significantly higher than those in groups A1 and B. HSP47/HSP70-positive cells were mesothelial cells, adipocytes, and alpha-SMA-positive myofibroblasts. Furthermore, the expression level of HSP47 was significantly higher in peritoneal specimens from patients with refractory peritonitis than without it and was significantly higher in patients with more than 60 months of CAPD therapy than that in patients with less than 60 months of CAPD. CONCLUSION: Our results indicate that CAPD therapy may induce HSPs in the peritoneal tissue, and that peritonitis in CAPD patients may be associated with the progression of peritoneal sclerosis at least through HSP47 expression and chronic macrophage infiltration. Our data also suggest that the progression of peritoneal sclerosis in such patients is associated with deterioration of peritoneal ultrafiltration function.     

Inherited factor H deficiency and collagen type III glomerulopathy

A non-immune complex-mediated glomerulonephritis associated with persistent hypocomplementemia occurred in a young boy. Measurement of complement components revealed complete factor H deficiency, inherited as an autosomal recessive trait. Evaluation of the renal lesion revealed extensive deposition of type III collagen suggestive of collagen type III glomerulopathy, a recently identified cause of chronic renal insufficiency in children and adults. This report represents the first association of inherited factor H deficiency with collagen type III glomerulopathy.     

Collagen type III glomerulopathy: a new type of hereditary nephropathy

A new type of hereditary glomerulopathy was observed in ten children presenting with early and progressive glomerular symptoms, often associated with hypertension. Light microscopy showed a diffuse increase in the mesangial matrix and generalized widening of the capillary walls. Electron-microscopic examination of renal tissue, after phosphotungstic acid treatment, revealed the presence of fibrillar collagen within the mesangial matrix and the subendothelial aspect of the glomerular basement membrane, adjacent to normal lamina densa. Immunohistochemical studies identified the fibrillar collagen not usually present within the glomerular extracellular matrix as type III collagen. Clinical and family studies ruled out the diagnosis of nail-patella syndrome, an autosomal dominant disorder with typical extrarenal symptoms, which is also characterized by the presence of fibrillar collagen within the glomerular basement membranes. The poor renal outcome, the possible extrarenal haematological and pulmonary involvement and the transmission as an autosomal recessive trait strongly suggest that collagen type III glomerulopathy is a new type of hereditary disease. From the high incidence of superimposed haemolytic uraemic syndrome in patients or their siblings, it may be hypothetized that collagen type III glomerulopathy is the underlying defect in some of the familial cases of haemolytic uraemic syndromes.     

Familial nephropathy and multiple exostoses with exostosin-1 (EXT1) gene mutation

Glomerular deposition of fibrillar collagen is a characteristic finding of genetically distinct conditions, including nail-patella syndrome and collagen type III glomerulopathy. A case of familial nephropathy in which steroid-sensitive nephrotic syndrome and glomerular deposits of fibrillar collagen are associated with multiple exostoses due to mutation of the EXT1 gene is described. This gene encodes a glycosyltransferase required for synthesis of heparan sulfate glycosaminoglycans. There is deficiency of heparan sulfate and perlecan, together with accumulation of collagens, in the matrix of EXT1-associated osteochondromas. Similar glomerular basement membrane abnormalities could offer an explanation for both the renal ultrastructural changes and steroid-sensitive nephrotic syndrome.     

Advanced glycation end-products and peritoneal sclerosis

Long-term continuous ambulatory peritoneal dialysis (CAPD) often causes peritoneal fibrosis and sclerosis with a loss of function, and some CAPD patients develop sclerosing encapsulating peritonitis. Glucose-based peritoneal dialysis fluids readily produce glucose degradation products by heat sterilization, and glucose degradation products accelerate the formation of advanced glycation end-products (AGE) in the peritoneal cavity. The accumulation of AGE is observed in peritoneal mesothelial and submesothelial layers in CAPD patients, accompanied by enhanced expression of various growth factors and peritoneal thickening. The expression of transforming growth factor-beta1 (TGF-beta1), macrophage-colony stimulating factor, and vascular endothelial growth factor (VEGF) is distributed in the peritoneum similarly to that of AGE. In CAPD patients with low ultrafiltration (UF) capacity, peritoneal membrane is thickened owing to an increase in the number of cells such as fibroblasts and macrophages and collagen in the submesothelial layer. AGE is detected in the fibroblasts and macrophages as well as degenerated collagen. These cells in the submucosal layer are almost positive for the receptor for AGE (RAGE) and uptake AGE. The intensity of AGE accumulation and the expression of growth factors are associated with the severity of UF impairment. In fact, the accumulation of AGE and the expression of growth factors are recognized most markedly in the peritoneum of CAPD patients with low UF and sclerosing encapsulating peritonitis. In conclusion, long-time CAPD with heat-sterilized peritoneal dialysis fluid promotes AGE accumulation in the peritoneal membrane and alteration in peritoneal cell function and dialysis quality, followed by peritoneal sclerosis, and, finally, sclerosing encapsulating peritonitis.     

Efficacy of Targeted Complement Inhibition in Experimental C3 Glomerulopathy

C3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy.     

Familial fibronectin glomerulopathy: analysis of chromosome 1q32 and uteroglobin gene loci in a large New Zealand family

SUMMARY: Recently, a newly recognized familial glomerulopathy with predominant fibronectin deposits has been reported. This is the first report of a family with this condition in Australasia and spans two generations over a 30‐year period, with the histologically confirmed glomerulopathy present in the father and five out of eight siblings. The clinical presentations have ranged from asymptomatic proteinuria, pregnancy‐associated proteinuria and the nephrotic syndrome to hypertension and proteinuria with progressive renal failure. The time‐course from presentation to renal failure was over a 20 years. Histology demonstrated global and diffuse thickening of capillary loops, but no cellular proliferation. Immunofluorescence demonstrated granular positivity for IgM in the capillary loops only. Electron microscopy demonstrated massive electron‐dense subendothelial granular deposits with occasional small fibrils and unremarkable epithelial cell foot processes. Immunohistochemical staining was strongly positive for fibronectin and negative for type I or type IV collagen and transforming growth factor β in all biopsies. Genetic studies of familial fibronectin glomerulopathy have recently highlighted two genetic loci. Firstly, a large five‐generation pedigree has been described with linkage of fibronectin glomerulopathy to chromosome 1q32. Secondly, fibronectin glomerulopathy has been reported in uteroglobin gene knockout mice. In our studies, DNA sequence analysis of the uteroglobin gene showed that it was normal in all family members, and a DNA polymorphism in the uteroglobin gene did not co‐segregate with the disease. In addition, DNA microsatellite markers at the 1q32 locus did not co‐segregate with the disease in our family. We presume that the underlying abnormality involves as yet undefined glomerular extracellular matrix regulation and is inherited as an autosomal dominant condition. These data favour genetic heterogeneity for the aetiology of fibronectin glomerulopathy.     

Abnormal lipoprotein and apolipoprotein pattern in lipoprotein glomerulopathy

Recently, two cases of renal disease were observed in which there was an abnormal accumulation of lipids, "lipoprotein thrombi," in the glomerular capillary lumen. This disease has been designated as lipoprotein glomerulopathy. Four other cases have been diagnosed independently by renal histology in other clinical laboratories. All six patients showed proteinuria (1.6 to 10 g/d), normal lecithin-cholesterol acyltransferase (LCAT) activity, type III hyperlipoproteinemia-like lipoprotein profiles, and significantly (P less than 0.01) higher levels of plasma apolipoprotein (apo) E (greater than 10 mg/dL) compared with the control patients with hyperlipidemic nephrotic syndrome without lipoprotein thrombi and type IIb hyperlipoproteinemia without renal disease. Lipoprotein glomerulopathy is not familial type III hyperlipoproteinemia (dysbetalipoproteinemia), because apolipoprotein E3 is present. Apo E isoforms were all rare: five cases of E2/3 and one case of E4/4. These results suggest that excessive apo E is associated with apo E isoform and lipoprotein metabolic derangement in such a renal disease. Further studies are needed on the relationship between the apo E hyperlipoproteinemia and the formation of lipoprotein thrombi.     

Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim)

BACKGROUND: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proalpha2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, alpha1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, alpha1(I)2alpha2(I). Previous studies of the oim/oim mouse have focused on the musculoskeletal system, with no systematic evaluation of other organ systems. METHODS: Multiple tissues from oim/oim, oim/+ (heterozygous) and +/+ (wild-type) mice were examined for gross and histological abnormalities. Tissues were stained with (1) hematoxylin and eosin (to assess lesion formation), (2) picrosirius red (collagen content), and (3) periodic acid methenamine silver (basement membrane). Kidneys were further evaluated ultrastructurally by electron microscopy and immunohistochemically with anti-alpha1(I) and anti-alpha1(III) collagen antibodies. RESULTS: Histological analyses revealed accumulations of picrosirius red-positive material, consistent with collagen, in glomeruli of 28/29 oim/oim mice, with no evidence of mesangial cell proliferation. Only the most severely affected animals had evidence of increased capillary basement membrane thickening or mild inflammation around the affected glomeruli. Electron microscopy confirmed the presence of fibrillar collagen. Immunohistochemistry with anti-alpha1(I) collagen antibodies confirmed accumulation of type I collagen in the oim/oim glomeruli. The +/+ and oim/+ kidneys had normal mesangium with no evidence of infiltration of collagenous material. CONCLUSIONS: This study demonstrates the first evidence, to our knowledge, of abnormal glomerular collagen deposition associated with a type I collagen defect. Further in vivo and in vitro studies are necessary to elucidate the mechanistic, functional, and pathological significance of the oim/oim collagen glomerulopathy.     

Antisense oligonucleotides against collagen-binding stress protein HSP47 suppress peritoneal fibrosis in rats

BACKGROUND: Peritoneal fibrosis is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD), but the molecular mechanism of this process remains unclear. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules, and is expressed in the tissue of human peritoneal fibrosis. In the present study, we examined the effect of HSP47 antisense oligonucleotides (ODNs) on the development of experimental peritoneal fibrosis induced by daily intraperitoneal injections of chlorhexidine gluconate (CG). METHODS: HSP47 antisense or sense ODNs were injected simultaneously with CG from day 14, after injections of CG alone. Peritoneal tissue was dissected out 28 days after CG injection. The expression patterns of HSP47, type I and type III collagen, alpha-smooth muscle actin (alpha-SMA), as a marker of myofibroblasts, ED-1 (as a marker of macrophages), and factor VIII were examined by immunohistochemistry. RESULTS: In rats treated with CG alone, the submesothelial collagenous compact zone was thickened, where the expression levels of HSP47, type I and type III collagen and alpha-SMA were increased. Marked macrophage infiltration was also noted and the number of vessels positively stained for factor VIII increased in the CG-treated group. Treatment with antisense ODNs, but not sense ODNs, abrogated CG-induced changes in the expression of HSP47, type I and III collagen, alpha-SMA, and the number of infiltrating macrophages and vessels. CONCLUSION: Our results indicate the involvement of HSP47 in the progression of peritoneal fibrosis and that inhibition of HSP47 expression might merit further clinical investigation for the treatment of peritoneal fibrosis in CAPD patients.     

The Ehlers-Danlos specter revisited

Ehlers-Danlos type IV is a major concern to vascular surgeons because it is often associated with spontaneous hemorrhage from arteries containing decreased type III collagen. Five members of a family with Ehlers-Danlos type IV and a review of another family of five with Ehlers-Danlos type IV are reported. Evaluation of the recent family included clinical evaluation as well as assay of collagen production. The age range of the three involved females and two males was 7 to 52 years. The father of the affected family had a spontaneous colon perforation at age 39. His son, at age 27, had a spontaneous rupture of the iliac artery. Revascularization was accomplished with difficulty. His daughter had a large cerebral bleed. Two granddaughters, ages 7, have not had any bleeding or aneurysmal events. The amount of type III collagen was only 10% of normal in the patient with the iliac artery rupture. The three females all exhibited similarly low levels of type III collagen. The father's type III collagen level was not sufficiently low to confirm Ehlers-Danlos type IV, although he had a spontaneous colon perforation. In the other Ehlers-Danlos type IV family of five, the three surviving members had type III collagen levels as low as 5% of normal. Two family members died after spontaneous iliac rupture at ages 24 and 33. Both families exhibited an autosomal dominant inheritance pattern. Ehlers-Danlos type IV remains a challenging problem for vascular surgeons. It is transmitted as an autosomal dominant inheritance with a high degree of penetrance. Spontaneous arterial and intestinal perforations should alert the clinician to the possibility of Ehlers-Danlos type IV. Patients should be evaluated noninvasively. Arterial repairs may not be successful in these patients because the vessels are extremely friable. Assays of collagen production are advisable in establishing the diagnosis.     

Collagen biosynthesis in normal and hypertrophic scars and keloid as a function of the duration of the scar.

The rates of collagen biosynthesis and the tissue concentrations of collagen in normal scar, hypertrophic scar and keloid were determined as a function of the duration of the lesions. The rate of collagen synthesis in normal scar was approximately constant between 6 months and 20 years after the initial wounding, but in both hypertrophic scar and keloid the rate was initially approximately twice that in normal scar, and 2-3 years after wounding it fell to approximately the same level as in normal scar. The tissue concentration of collagen appeared to be relatively constant in normal scar with respect to the time elapsed after wounding, but in both types of abnormal scar it was initially somewhat lower than normal scar and then rose to values higher than in normal scar after about 2-3 years. Since similar results were obtained for both types of abnormal scar in terms of the rates of collagen biosynthesis with respect to the time elapsed after wounding and also in terms of the tissue concentrations of collagen, this may indicate that the events in the pathogenesis of both abnormal scar types are similar. The results also raise the possibility that the formation of both types of abnormal scar may occur in two phases: an initial phase characterized by abnormally high rates of collagen biosynthesis and a later phase characterized by essentially normal rates of collagen biosynthesis.     

Aneurysm or occlusive disease--factors determining the clinical course of atherosclerosis of the infrarenal aorta.

Atherosclerosis of the infrarenal aorta results in distinct clinical entities--aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA). Although loss of collagen has been implicated in AAA, collagen accumulation plays a role in AOD. In vivo collagen-gene expression can be assessed using complementary DNA for collagen types I and III alpha-chains. The purpose of this study is to compare total collagen (type I + III) and collagen types I and III messenger RNA in AAA, AOD and normal aorta. Specimens were collected from the infrarenal aorta during operation for AOD (n = 7), AAA (n = 7), autopsy, or organ procurement (normal; n = 7). Northern transfer analysis of total RNA was used to compare mRNA levels for type I and III collagen. After preliminary extraction, specimens were hydrolyzed for hydroxyproline analysis used to calculate total collagen (type I + III). Relative levels of type I (pro-a1[1]) mRNA were greater in both AOD (0.77 +/- 0.35) and AAA tissue (0.94 +/- 0.24; p = 0.6) than in normal aorta (0.02 +/- 0.03). Type III (pro-a1[III]) mRNA levels were also greater in AOD (2.52 +/- 0.19; p = 0.09) and AAA tissue (3.15 +/- 1.3) than in normals (0.97 +/- 0.47). Total collagen concentration was increased in AOD (45.6% +/- 3.1% dry weight; p less than 0.05) but not AAA tissue (27.8% +/- 4%) when compared to normal aorta (34.7% +/- 2.3%). Collagen type I and III gene expression is greater in older, diseased aorta, yet collagen accumulated only in AOD. This implies a similar synthetic response in both AOD and AAA. Thus, proteolytic degradation in AAA appears to determine collagen content and possibly the clinical course of the atherosclerotic process.     

Acute and Chronic Vascular Rejection in Nonhuman Primate Kidney Transplantation

A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days post-transplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals. In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR.     

Pleuroperitoneal communication detected at the beginning of continuous ambulatory peritoneal dialysis; report of a case

A 61-year-old female was diagnosed as having end-stage renal failure developed dyspnea soon after introduction of continuous ambulatory peritoneal dialysis (CAPD). Chest X-ray showed a right-side massive pleural effusion. Pleuro peritoneal communication was suspicious, because the hydrothorax significantly improved by the stop of CAPD. We performed video-assisted thoracic surgery. Using indigo carmine containing peritoneal dialysis fluid through a CAPD catheter, we found a fistula on the diaphragm from which blue dialysis solution flowed out like a fountain. The fistula of the diaphragm was directly closed with a surgical stapler and covered using cellulose oxidized (Surgicel) and fibrin glue. She could restart CAPD on postoperative days 7, and no recurrence of hydrothorax has been detected for 10 months after surgical treatment.     

Surgical correction of hydrothorax from diaphragmatic eventration in children on peritoneal dialysis

Continuous ambulatory peritoneal dialysis (CAPD) is frequently used in the pediatric age group for reversible and end-stage renal failure. Most pediatric patients tolerate this therapy with few complications. Approximately 2% of children, however, develop massive unilateral hydrothorax. This major complication usually results in the discontinuation of peritoneal dialysis in all forms and the institution of hemodialysis. Occult diaphragmatic defects account for most adult and pediatric patients who develop this complication. Three pediatric patients receiving CAPD complicated by massive hydrothorax are described. All patients were successfully treated by thoracotomy and repair of the diaphragmatic eventration with an immediate return to CAPD. This is the first report of successful therapy of this kind in children. A review of the cause, diagnosis, and treatment of massive hydrothorax developing during CAPD therapy is presented.