Renal involvement in genetic disease

There are more than 200 inherited disorders in which the kidney is affected and which display a wide range of renal features. Autosomal dominant polycystic kidney disease— affects about 1/1000 individuals and accounts for 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 75% of cases and mutations in polycystin 2 accounting for most of the remainder. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure between 40 and 80 years of age. Main extrarenal manifestations are intracranial aneurysms, liver cysts, and mitral valve prolapse. Alport’s syndrome—X-linked dominant inheritance in 85% of kindreds, with molecular defects involving the gene encoding the α‎-5 chain of the type IV collagen molecule. Males typically present with visible haematuria in childhood, followed by permanent nonvisible haematuria, and later by proteinuria and renal failure. Extrarenal manifestations include perceptive deafness of variable severity and ocular abnormalities. Carrier women often have slight or intermittent urinary abnormalities, but may develop mild impairment of renal function late in life, and a few develop endstage renal disease. In the autosomal recessive form of Alport’s syndrome, renal disease progresses to endstage before 20 to 30 years of age at a similar rate in both affected men and women. Other disorders covered in this chapter include hereditary tubulointerstitial nephritis, hereditary tumours, glomerular structural diseases, metabolic diseases with glomerular involvement (Fabry’s disease), congenital anomalies of the kidney and urinary tract, and other genetic diseases with kidney involvement.

Undertreatment of Disease Activity in Systemic Lupus Erythematosus Patients with Endstage Renal Failure Is Associated with Increased All-cause Mortality

Objective.In a cohort of systemic lupus erythematosus (SLE) patients with endstage renal failure, to evaluate whether continuing rheumatology followup visits and immunosuppressive therapy after starting renal replacement were associated with increased survival.Methods.We identified all SLE patients over 21 years old who started renal replacement therapy between 2005 and 2011 at an urban tertiary care center. Mortality data were obtained using in-hospital records and the US Social Security Death Index database.Results.We identified 80 SLE patients undergoing renal replacement therapy. Twenty-two patients (28%) were followed in rheumatology clinics frequently (2 or more visits per year) after starting renal replacement therapy, and 58 patients (72%) were followed infrequently (fewer than 2 visits per year). Survival rates were significantly higher in transplant patients compared with dialysis patients. Patients with SLE followed frequently after starting dialysis had significantly higher 4-year survival rates compared with patients followed infrequently after starting dialysis (log-rank p = 0.03). In the Cox proportional hazards model, treatment with prednisone alone or with no medication was associated with a hazard ratio (HR) of death = 6.1 (95% CI 1.1, 34; p = 0.04) and HR = 13 (95% CI 1.5, 106; p = 0.02), respectively, compared with patients treated with a combination of immunosuppressive therapy with or without prednisone, adjusted for age at SLE diagnosis, sex, transplant status, and the frequency of rheumatology visits after the development of endstage renal failure.Conclusion.Active disease in patients with SLE undergoing renal replacement therapy may be underrecognized and undertreated, leading to increased mortality.

Renal involvement in genetic disease

There are many inherited disorders in which the kidney is affected: this chapter is concerned with the commonest inherited diseases leading to renal failure. Autosomal dominant polycystic kidney disease—accounts for about 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 85% of cases and mutations in polycystin 2 accounting for most of the remainder, these being transmembrane proteins that are able to interact, function together as a nonselective cation channel, and also induce several distinct transduction pathways. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure at between 40 and 60 years of age. Extrarenal manifestations include intracranial aneurysms, liver cysts, and mitral valve prolapse....