Transplantation for polycystic kidney disease

During the 4-year period from June 1977 to May 1981, a total of 108 patients with polycystic kidney disease and 2440 nonpolycystic patients received cadaver renal allografts in the Southeastern Organ Procurement Foundation (SEOPF) Prospective Study. There were no significant differences between the groups with and without polycystic disease in terms of recipient blood group, history of splenectomy, or preformed antibody status. As a group, transplanted polycystic patients underwent native nephrectomy more often, had a better HLA match, received less antilymphocyte serum (ALS), and were slightly older than nonpolycystic patients. Although proportionately fewer polycystic patients received pretransplant transfusions than nonpolycystic patients (P = .002), transfusion was associated with a significant increase in graft survival in the polycystic group (P less than .05), as well as in the nonpolycystic group (P less than .0001). Gene frequency analysis showed no HLA-A, or -B antigen linkage with polycystic disease. No significant differences existed between the polycystic and nonpolycystic groups in terms of overall graft and patient survival. However, transplanted polycystic patients died more frequently from bacterial sepsis (P less than .05), especially from gram-positive organisms (P = .01). Pretransplant bilateral nephrectomy did not affect the incidence of sepsis. However, following graft failure, patients with bilateral native nephrectomy had a greater incidence of severe anemia (50% versus 39%) and death (58% versus 25%; P less than .05) than those with unilateral nephrectomy or no nephrectomy. Treatment with ALS did not significantly improve graft survival in those with polycystic disease. A strong positive correlation was found between patient death and treatment with ALS only in the polycystic group (P less than .01). These findings indicate that the use of pretransplant bilateral native nephrectomy and posttransplant ALS should be judicious in the polycystic patient because they may be associated with increased morbidity and mortality.     

Transplantation of a cadaveric polycystic kidney in a patient with autosomal dominant polycystic kidney disease: long-term outcome

INTRODUCTION: Kidneys from donors affected by autosomal dominant polycystic kidney disease (ADPKD) were considered unusable for transplantation. To the best of our knowledge, seven cases worldwide have now been described in the English literature since 1967 suggesting such donor organs may be acceptable under certain conditions. Most of these reports have only short-term follow-up. METHODS: We provide a review of these patients and share our experience with an ADPKD patient who had a cadaveric ADPKD transplant and has been closely followed for 10 years. RESULTS: During the 10-year period, the patient had three transplant biopsies without complication. This creatinine is currently 1.2 mg/dL. Serial computed tomography imaging indicated that the cystic disease slowly progressed during this time period. He eventually developed intractable pain in his native left kidney and underwent a laparoscopic nephrectomy. CONCLUSIONS: Normal functioning cadaveric kidneys that show early signs of polycystic kidney disease should be considered acceptable for renal donation. These organs provide the recipient a safe, reasonable period of graft survival and have not been shown to cause adverse effects.     

Treatment prospects for autosomal-dominant polycystic kidney disease

An increased understanding of the molecular genetic and cellular pathophysiologic mechanisms responsible for the development of autosomal-dominant polycystic kidney disease (ADPKD), made possible by the advances in molecular biology and genetics of the last three decades, has laid the foundation for the development of effective therapies. As the concept that a polycystic kidney is a neoplasm in disguise is becoming increasingly accepted, the development of therapies for ADPKD may benefit greatly from the expanding body of information on cancer chemoprevention and chemosuppression. This review summarizes the observations that already have been made and discusses therapies for PKD that deserve investigation.     

Renal transplantation for end-stage polycystic kidney disease

From 1963 to 1984, 56 renal transplants were performed in 51 patients with end-stage renal failure due to autosomal dominant polycystic kidney disease (ADPKD). There were 49 cadaver and 7 living-related transplants. Overall patient and graft survival was 88 per cent and 66 per cent at one year, 59 per cent and 49 per cent at five years, respectively. There was no significant difference in patient or graft outcome with cadaver versus living-related donor kidneys. One-year graft success with and without pretransplant bilateral nephrectomy (BN) was 78 per cent versus 58 per cent, respectively (n.s.). Patient survival after return to dialysis after graft loss was not compromised by the earlier performance of BN. In patients who did not undergo pretransplant BN, there were no complications from the retained native kidneys after transplantation. In cadaver recipients, the two-year graft success rate with and without preliminary blood transfusions was 54 per cent versus 61 per cent, respectively (n.s.). Cadaver graft survival with and without adjunctive antilymphocyte globulin (ALG), excluding 3 recipients managed with cyclosporine, was 88 per cent versus 50 per cent at one year, and 70 per cent versus 32 per cent at five years, respectively (p less than 0.05). This beneficial effect of ALG was still evident when only transfused cadaver recipients were analyzed and was achieved with no resulting compromise in patient survival. Follow-up computerized tomography (CT) scanning of the transplant kidney in 10 recipients with a long-term (1-9 years) functioning allograft showed no evidence of recurrent ADKPKD.     

Diverticulitis and polycystic kidney disease

Patients with adult polycystic kidney disease (PKD) have previously been shown to have an increased incidence of complicated diverticulitis after renal transplantation. The purpose of this study was to assess the risk of diverticulitis in the PKD population. We retrospectively reviewed patients with advanced PKD, defined as end-stage renal failure requiring dialysis. Patients were obtained from a single nephrology group practice between January 1985 and January 1997, or from all patients being evaluated or actively considered for renal transplantation at our institution as of May 1997. The incidence and severity of diverticulitis in these patients was compared with that observed in a similar cohort of patients with end-stage renal disease due to other etiologies. The study population consisted of 184 renal failure patients, 59 with PKD and 125 with other causes of end-stage renal disease. Twelve (20%) patients with PKD had a history of active diverticulitis, whereas only 4 (3%) of the non-PKD controls had diverticulitis (P = 0.0003, Fisher's exact test). Six of the 12 PKD patients required surgical intervention. Patients with renal failure due to PKD experience a significantly higher rate of diverticulitis than do other patients with end-stage renal disease. Furthermore, diverticulitis is frequently severe in PKD patients, with 50 per cent requiring surgical intervention. These data suggest that diverticular disease may be an extrarenal manifestation of polycystic kidney disease.     

Autosomal recessive polycystic kidney disease

The clinical features of 55 cases of autosomal recessive polycystic kidney disease (ARPCKD) have been reviewed. Each had evidence of ARPCKD. The outcomes of 87% were known; 24 had died. Twenty-four of 31 were seen between 1980 and 1986; 7 could not be traced. Forty-five percent presented under 1 month; 38% between 1 month and 1 year; and 9 cases over 1 year. Hyponatraemia occurred in 15 out of 19 aged less than 3 months; hypertension occurred in 65%; splenomegaly in 47% of those surviving more than 3 months. Portocaval shunts were done in 5 aged 2–12 years. Thirteen died of renal failure, 6 under 1 year, and 7 between 1 year and 13 years. Life-table survival rates calculated from birth revealed that 86% were alive at 3 months, 79% at 1 year, 51% at 10 years, and 46% at 15 years. Calculations based on patients who survived to 1 year of age showed that 82% were alive at 10 years and 79% at 15 years. These results reveal an improved prognosis for a condition once assumed to be fatal.Presented in part at the Xth International Congress of Nephrology, London, UK, July 1987, and at the Canadian Pediatric Society, Montreal, Canada, July 1987     

Congenital murine polycystic kidney disease

In the current study, the pathogenesis of proximal tubular cyst formation was studied in an animal model of polycystic kidney disease, the CPK mouse. The specific roles of (a) sodium-potassium adenosine triphosphatase (Na–K ATPase) activity, determined by an enzyme-linked kinetic microassay, (b) proximal tubular epithelial hyperplasia, determined by calculation of mitotic indices, and (c) altered proximal tubular basal lamina formation, determined by immunohistological localization of basal lamina glycoproteins, were investigated at progressive developmental stages of CPK proximal tubular cyst formation. Increases in renal Na–K ATPase were present at the earliest fetal stages of proximal tubular cyst formation, and subsequently paralleled the course of proximal tubular cyst progression. Proximal tubular epithelial hyperplasia, although not present at the earliest stages of cyst formation, was a consistent feature of progressive proximal tubular cystic enlargement. Abnormalities in basal lamina glycoprotein expression were not present at any stage of proximal tubular cyst development. We conclude that increased Na–K ATPase and tubular epithelial hyperplasia are significant features of proximal tubular cyst formation in the CPK mouse.     

Congenital murine polycystic kidney disease

In the current study, the ontogeny of tubular cyst formation was studied in the CPK mouse, a murine strain with autosomal recessive polycystic kidney disease. Utilizing the technique of intact nephron microdissection in addition to standard light and transmission electron microscopy, the earliest morphologic alterations in CPK kidneys were localized in fetal tissue at 17 days of gestation to the distal portion of developing proximal tubules. During disease progression, from birth to 21 days of postnatal age, there was a shift in the site of cystic nephron involvement from proximal tubule to collecting tubules without involvement of other nephron segments. Cysts were enlarged tubular segments which remained in continuity with other portions of the nephron and were not associated with abnormalities in the overall pattern of nephron growth or differentiation. Analysis suggested that alterations in transtubular transport in abnormally shortened proximal tubular segments of juxtamedullary nephrons may have pathogenic importance in the early stages of cyst formation, and that epithelial hyperplasia and cytoskeletal alterations may have a role in progressive proximal tubular cystic enlargement. Cellular hyperplasia of epithelial walls of normally formed tubules was a prominent feature of cyst formation and progressive enlargement in collecting tubules. Such data form the basis for future studies into specific pathophysiological processes which may be operative in specific nephron segments during different stages of cyst formation in the CPK mouse.A preliminary report of this work was presented at the Annual Meeting of the Society for Pediatric Research, Washington DC, USA, May 1986, and has appeared in abstract form (Pediatr Res 20: 446A, 1986)     

Citrate therapy for polycystic kidney disease in rats

BACKGROUND: Few treatments are available to slow the progression to renal failure in autosomal dominant polycystic kidney disease (PKD). In an animal model of PKD, the male heterozygous Han:SPRD rat, intake of a solution of potassium citrate plus citric acid (KCitr) from age one to three months prevented a decline in glomerular filtration rate (GFR). The present study tested whether this beneficial effect is sustained and explored handling of citrate and ammonia in normal and cystic kidneys. METHODS: Rats were provided with tap water or citrate solutions to drink, and clearance and survival studies were performed. RESULTS: The GFRs of rats with PKD that consumed KCitr from one month of age were normal at six months of age, while those of their counterparts on water were about one third of normal. Long-term KCitr treatment extended the average life span of rats with PKD from 10 to 17 months. Compared with normal rats, water-drinking rats with PKD had higher plasma [citrate], renal cortical [citrate], and fractional excretion of citrate, and lower rates of renal citrate consumption, ammonia synthesis, and ammonia excretion. Cortical PNH3 was not elevated in cystic kidneys. Intake of Na3 citrate/citric acid solution or K3 citrate solution, but not ammonium citrate/citric acid solution, prevented a decline in GFR in three-month-old rats with PKD. CONCLUSIONS: Rats with PKD show abnormal renal handling of citrate and ammonia. Citrate salts that have an alkalinizing effect preserve GFR and extend survival.     

Von Hippel-Lindau disease simulating polycystic kidney disease

Polycystic kidney disease and the renal manifestations of von Hippel-Lindau disease have much in common. Making the distinction between these two diseases is important. There is a strong association of renal cell carcinoma with von Hippel-Lindau disease, whereas renal cell carcinoma is rare in polycystic kidney disease. Furthermore, the many extrarenal manifestations of von Hippel-Lindau disease are serious and can be fatal while those of polycystic kidney disease are generally benign. Early diagnosis of the lesions of von Hippel-Lindau disease could lead to effective surgical treatment and prevent death. A case of von Hippel-Lindau disease is presented which was incorrectly diagnosed as polycystic kidney disease for sixteen years. The case is instructive in that the possibility of making the correct diagnosis prior to the patient's terminal illness was only through careful assessment of the family. The case is also remarkable in that the patient suffered from progressive renal failure requiring hemodialysis, which has not been associated previously with von Hippel-Lindau disease.     

Therapeutic interventions for autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the United States and causes end-stage renal failure requiring dialysis and renal transplantation. There is no effective treatment for ADPKD in humans. However, there are now multiple clinical trials testing a host of therapeutic interventions in children and adults with ADPKD. The major therapeutic interventions being tested in patients with ADPKD include Tolvaptan, Octreotide, Sirolimus, Everolimus, and statins, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).     

Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease

Background The authors reviewed their experience with laparoscopic nephrectomy for autosomal dominant polycystic kidney disease to evaluate whether patient-related or surgery-related factors influence operative outcomes.Methods A retrospective review was carried out of 22 consecutive laparoscopic nephrectomies performed by one surgeon in a university setting between March 1998 and March 2003. The impact of patient factors (body mass index, preoperative hemoglobin level, preoperative blood urea nitrogen and creatinine, kidney size and side, prior abdominal surgery, dialysis) and surgical factors (surgeon experience and preoperative embolization) on short-term outcomes (estimated blood loss, transfusion requirements, operative time, conversion, intra- and postoperative complications and length of stay) was analyzed using the Students t-test, Pearson correlation, and Mann–Whitney and Fisher tests.Results A total of 19 patients underwent 22 nephrectomies. The average patient age was 49 years (range, 36–65 years) and the average body mass index was 31.4 kg/m² (range, 20.4–64.5 kg/m²). Fourteen patients (68%) were receiving dialysis. Fifteen right (68%) and 7 left (32%) nephrectomies were performed. The median kidney size was 22 cm (range, 8–50 cm). Five patients (23%) had preoperative embolization. The median operative time was 255 min (range, 95–415 min). There were no mortalities. The intraoperative complication rate was 18% (1 vena cava laceration, 1 cecal perforation, 1 dialysis fistula thrombosis, 1 intrarenal bleeding requiring conversion), and the postoperative complication rate was 32% (1 myocardial infarction, 1 urgent laparotomy for clinical peritonitis, 1 minor bile fistula, 1 AV fistula thrombosis, 2 incisional hernias, 1 urinary retention). Four procedures (18%) were converted (1 for vena cava laceration, 1 for cecal perforation, 1 for intrarenal bleeding, 1 for adhesions). The median blood loss was 400 ml (range, 100–5000 ml). Eight patients (36%) received transfusions (median, 2 units). The median length of stay was 4 days. The patients who required blood transfusions had lower preoperative hemoglobin levels. Preoperative embolization did not affect surgical outcome. However, surgeon experience significantly reduced operative time.Conclusions Laparoscopic nephrectomy for autosomal dominant polycystic kidney disease is a safe procedure, providing patients with a short hospital stay. Complication and conversion rates are relatively high.Presented at the 11th International Congress of the European Association for Endoscopic Surgery and other Interventional Techniques (EAES), Glasgow, 15–18 June 2003