Monogenic causes of chronic kidney disease in adults.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

Managing acute and chronic renal stone disease.

Nephrolithiasis, or renal stone disease, is common and the incidence is increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a population level, the increase in stone incidence, erosion of gender disparity, and younger age of onset is likely to reflect increasing prevalence of obesity and a Western diet with a high intake of animal protein and salt. Stones can be detected by a variety of imaging techniques. The gold standard is a non-contrast CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones. CT KUB should be the primary mode of imaging for all patients with colic unless contraindicated. In such instances, or if a CT KUB is not available, an ultrasound KUB is an alternative. This has advantages in terms of radiation exposure and cost, but is limited in sensitivity, particularly for ureteric stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque stones. For most patients diclofenac is a reasonable first choice of analgesia, e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be less effective, but should be used if there is a contraindication to NSAIDs. A combination of diclofenac, paracetamol, and/or codeine regularly can provide adequate pain control in many cases. Failure of this analgesic combination should prompt consideration of secondary care support. If a ureteric stone < 5 mm in diameter is identified, the expectation is that this will pass without intervention. Initially medical management is still useful for stones between 5 and 10mm in diameter, but urology input is more likely to be necessary as up to 50% of these may require intervention. Stones that are >10 mm in diameter should be discussed with the urology service as they are unlikely to pass spontaneously.