Marginal parent donors-Process and ethics.

BACKGROUND: Pre-emptive kidney transplantation for end-stage kidney disease in children has many advantages and may lead to the consideration of marginal parent donors. METHODS: Using the example of the transplant of a kidney with medullary sponge disease from a parent to the child, we review the ethical framework for working up such donors. RESULTS: The four principles of health ethics include autonomy (the right of the patient to retain control over his/her own body); beneficence (healthcare providers must do all they can do to benefit the patient in each situation); non-maleficence ("first do no harm"-providers must consider whether other people or society could be harmed by a decision made, even if it is made for the benefit of an individual patient) and justice (there should be an element of fairness in all medical decisions). Highly motivated donors may derive significant psychological benefit from their donation and may thus be willing to incur more risk. The transplantation team and, ideally, an independent donor advocate team must make a judgment about the acceptability of the risk-benefit ratio for particular potential donors, who must also make their own assessment. The transplantation team and donor advocate team must be comfortable with the risk-benefit ratio before proceeding. CONCLUSIONS: An independent donor advocacy team that focuses on the donor needs is needed with sufficient multidisciplinary ethical, social, and psychological expertise. The decision to accept or reject the donor should be within the authority of the independent donor advocacy team and not the providers or the donor.

Hypertension in a patient with medullary sponge kidney: A case report.

RATIONALE: Medullary sponge kidney (MSK) is a congenital renal disorder characterized by recurrent nephrolithiasis or nephrocalcinosis. Recently, it has been found that MSK can be also combined with other diseases, such as primary aldosteronism and Beckwith-Wiedemann, but whether it is associated with secondary hypertension remains unknown. PATIENT CONCERNS: A 22-year-old hypertensive female presented to our hospital characterized by hypokalemia and hypertension. DIAGNOSIS: The laboratory examination showed secondary aldosteronism. And the common causes for secondary aldosteronism include renal artery stenosis, glomerulonephritis, lupus nephropathy, and diabetic nephropathy, all of which were excluded except MSK. INTERVENTIONS: She was treated with angiotensin-converting enzyme inhibitors. OUTCOMES: Her blood pressure, serum potassium, and plasma renin levels were reversed after treatment with angiotensin-converting enzyme inhibitors. LESSONS: We presumed that MSK may be associated with secondary hypertension, and the mechanism may be the activation of the renin-angiotensin-aldosterone system.

The impact of potassium citrate therapy in the natural course of Medullary Sponge Kidney with associated nephrolithiasis.

OBJECTIVES: The present study was carried out to evaluate the effectiveness of medical therapy with potassium citrate in preventing calculosis complicating Medullary Sponge Kidney (MSK) without renal acidification defects. MATERIALS AND METHODS: In a open, uncontrolled, retrospective analysis, 49 MSK patients with nephrolithiasis without renal tubular acidosis, underwent a complete metabolic evaluation and received potassium citrate therapy 4-6 g/day. The course of stone disease before and after citrate therapy was determined in each patient from a combination of clinical history, past records, radiographs and kidney ultrasound. The rate of new stone formation/pt/yr, of endourological and extracorporeal procedures, of urinary tract infection (UTI) and number of hospitalization before and after medical treatment were calculated. RESULTS: Metabolic anomalies (hypercalciuria, hypocitraturia, hyperuricuria and hyperoxaluria) were present in 83% of the patients. Follow-up before and after alkali citrate therapy was comparable (4.7+/-1.4 and 4.9+/-1.7 years respectively). Medical treatment significantly reduced rates of stone formation from 2.0+/-1.0 to 0.2+/-0.5 pt/yr, ureteroscopy (URS) from 0.9+/0.8 to 0.4+/-0.5 pt/yr, extratracoporeal lithotripsy (ESWL) from 1.1+/-0.8 to 0.4+/-0.6 pt/yr, urinary tract infections (UTIs) from 0.8+/-1.2 to 0.3+/-0.5 pt/yr and hospitalization from 1.1+/-0.6 to 0.2+/-0.3 pt/yr, p < 0.001. This effect was observed also in MSK patients without metabolic anomalies. In 35 patients the asymptomatic disappearance of calcium stones was also observed. CONCLUSIONS: Our study documents the effectiveness of potassium citrate therapy in preventing neprolithiasis in MSK patients also in the absence of distal tubular acidosis. It suggests that in MSK patients alkali citrate may promote calcium stone dissolution by oral administration.

Inherited renal diseases.

Genetic disorders of the kidney include cystic diseases, metabolic diseases and immune glomerulonephritis. Cystic diseases include autosomal dominant and recessive polycystic kidney disease (ADPKD, ARPKD, respectively). Neonates with enlarged, cystic kidneys should be evaluated for PKD. Patients with ADPKD have cysts and renal enlargement. Most patients present with hypertension, hematuria or flank pain; the most common extrarenal manifestation is polycystic liver disease. Oligohydramnios, bilaterally enlarged kidneys and decreased urine are featured in utero in ARPKD. Medullary sponge kidney is uncommon and features nephrocalcinosis, recurrent calcium stones and a history of polyuria/nocturia and/or urinary tract infections. Alport syndrome (AS) is an inherited disease of the glomerular basement membrane that is usually inherited as an X-linked dominant trait. Most patients with AS present in the first two decades of life with persistent microscopic or gross hematuria. Later, proteinuria is seen and its presence portends disease progression. Other findings may include sensorineural hearing loss and ocular abnormalities. There are various inherited tubulopathies, including Bartter syndrome, a group of renal tubular disorders that consist of two phenotypes with four genotypes. Patients usually present early in life with salt wasting, hypokalemia and metabolic alkalosis. Other features, depending on genotype, may include polyhydramnios and premature birth. Gitelman syndrome is also a salt-losing tubulopathy characterized by hypokalemic alkalosis. The majority of patients with Gitelman syndrome present during adolescence or early adulthood.

Adult renal cystic disease: a genetic, biological, and developmental primer.

Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases.

Lithiasis in cystic kidney disease and malformations of the urinary tract.

The prevalence of renal stones in renal cystic and malformative conditions exceeds the prevalence of renal stones in the general population, suggesting that the above-mentioned cystic and malformative disorders favor stone formation. Urinary stasis is generally assumed to play a major part in the pathogenesis of the nephrolithiasis associated with distorted renal anatomy due to a delayed washout of crystals and risk of urinary infections. However metabolic factors are also important in the pathogenesis of stones in these conditions. Indeed, metabolic abnormalities have been observed in the majority of stone-forming patients with conditions such as horseshoe kidney and ureteropelvic junction obstruction. Five different models of stone formation can be identified, depending on stone composition, risk of infection stones, and pathogenesis of renal cystic and malformative conditions. A proper metabolic evaluation should be conducted to diagnose specific, treatable metabolic disorders, thereby reducing the frequency of recurrent stone disease in these conditions as well.

Renal tubular dysfunction in patients with cystic disease of the kidneys.

OBJECTIVE: To define the renal tubular functional abnormalities in patients with cystic disease of the kidneys. METHODS: Patients with autosomal dominant polycystic kidney disease (ADPKD) (n = 4) and medullary sponge kidneys (MSK) (n = 3) with normal glomerular filtration rate (GFR), determined by inulin clearance, and effective renal plasma flow (ERPF), measured by p-aminohippurate clearance, underwent measurement of proximal and distal tubular functions. Proximal tubular functions were determined by the maximum reabsorption of glucose (TmGlucose) and the maximum secretion of p-aminohippurate (TmPAH). Distal tubular functions were measured by the maximum urinary concentrating and diluting mechanisms, and the urinary acidification response to acid load. RESULTS: TmGlucose was low in both groups (209 +/- 25 mg/min/1.73 m2 in the ADPKD group and 110 +/- 28 mg/min/1.73 m2 in the MSK, compared with 375 +/- 40 mg/min/1.73 m2 in healthy controls; P < 0.05). Likewise, TmPAH was significantly diminished in patients with ADPKD (72 +/- 6 mg/min/1.73 m2) and MSK (63 +/- 5 mg/min/1.73 m2) when compared with healthy controls (89 +/- 4 mg/min/1.73 m2; P < 0.05). Urinary maximum concentration after fluid deprivation was impaired in both ADPKD and MSK patients, but the diluting mechanism was intact. Finally, the ability to excrete urinary ammonium and titratable acids following an oral acid load was inadequate in both the ADPKD and MSK groups. CONCLUSIONS: Proximal and distal tubular functions are impaired in patients with ADPKD and MSK when GFR and ERPF are normal, indicating tubular disruption by the cysts and the alteration of the tubulo-interstitial vascular relationship.

Medullary sponge kidney associated with congenital hemihypertrophy.

Medullary sponge kidney is a developmental disorder characterized by ectatic and cystic malformation of the collecting ducts and tubules. Clinical manifestations include urinary tract infections, renal stones, and hematuria. It can be associated with other developmental disorders. A case of medullary sponge kidney associated with congenital hemihypertrophy, complicated by nephrocalcinosis and nephrolithiasis, is reported here.

Renal acidification defects in medullary sponge kidney.

Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine patients had some form of renal acidification defect; 8 had the distal type of renal tubular acidosis, 2 the complete and 6 the incomplete form. One patient had proximal renal tubular acidosis. These findings, which suggest that renal acidification defects play an important role in the pathogenesis of renal calculi in medullary sponge kidney, have considerable therapeutic implications.

Unilateral and segmental medullary sponge kidney: renal function and calcium excretion.

The renal acidification defect and renal hypercalciuria have been reported in patients with pan-renal and bilateral medullary sponge kidney. However, little is known about patients with unilateral or segmentally affected medullary sponge kidney. We report 2 cases of partially affected medullary sponge kidney with normal acidification ability and normal urinary calcium excretion, although the ability to concentrate urine was diminished. These findings suggest that in patients with partially affected medullary sponge kidney nephrolithiasis is not the consequence of renal hypercalciuria induced by systemic acidosis but is owing to the urinary stasis caused by cystic dilatation of the terminal collecting duct.

Medullary sponge kidney: abnormalities of renal tubular and glomerular function, and their relationship to clinical features.

This study confirms that medullary sponge kidney (MSK) has a good prognosis, but there is a considerable morbidity in patients with renal calcification; they suffer renal colic, ureteric obstruction, and frequently need operation. There is a high incidence of urinary infection in women. On follow-up, glomerular function is well maintained, although careful testing shows a mild depression of glomerular filtration rate in at least 40%. Proximal tubular function is normal, but abnormalities of distal tubular function are often seen: acidification defects occur in 24% and are associated with nephrocalcinosis, poor urine concentrating ability, and diminished glomerular function. Urine concentration defects occur in 73% and are probably secondary to nephrocalcinosis. Hypercalciuria was present in 19% and was not related to other defects.

Functional abnormalities in renal cystic diseases.

The functions of a kidney, whether normal or cystic, can be conceptualized in terms of anatomy (glomerulus, proximal tubule, loop of Henle, distal convolution, and collecting duct), activity (volume regulation, dilution and concentration, acid-base regulation, potassium excretion, transport of organic molecules, and calcium and phosphate excretion), and the integration of anatomic organization to meet functional demand. Our discussion of renal cystic disorders follows this conceptual outline. For discussions of normal renal physiology, the reader is referred to any one of several recent, excellent reviews (1-3). Systematic evaluation of renal function in cystic diseases of the kidney (medullary sponge kidney, medullary cystic disease, and polycystic kidney disease) has only rarely been performed. The available information suggests that the earliest detectable lesions consist primarily of tubular dysfunction. With time, however, significant reduction of glomerular filtration occurs and the resultant accumulation of uremic toxins dominates the clinical picture in polycystic and medullary cystic disease. Significant changes in glomerular function are unusual in medullary sponge kidney. This review represents an attempt to summarize the large body of literature that has accumulated on functional abnormalities in these disorders, and to point out those areas where further investigations are needed.

Alterations in renal tubular sodium and water transport in polycystic kidney disease.

Thirty patients with chronic renal diease -10 with polycystic kidney disease (PKD) and normal GFR; 10 with PKD and GFR is less than 30 ml+min; 10 with chronic glomerulonephritis (CGN) and GFR is less than 30 ml+min -and 10 normal subjects were investigated. The ability to concentrate urine maximally (T-CH2O) after water deprivation and the renal handling of water and electrolytes following hypertonic volume expansion were studied. A defect in T-CH2O was common in PKD patients even with normal GFR. In PKD patients with normal GFR, volume expansion was not followed by a natriuretic effect of the same magnitude as in controls. This ""inadequate natriuresis after volume expansion"" may be explained partly by chronic hyponatremia and partly by a functional defect, i.e. the incomplete arterial vasodilation in the kidney. At comparable degrees of renal insufficiency, T-CH2O was lower in PKD than in CGN patients. It seems likely that in PKD patients the increased endogenous osmotic load has exaggerated the tubular defect in urine concentration already present at normal GFR. Furthermore, volume expansion was followed by a significant increase in fractional sodium excretion only in PKD patients with renal insufficiency.