Table 4.

Examples of how genetic sequence data, along with clinical data, can be a valuable resource to guide personalized management

Impact of Management Examples
Influence choice of therapyRecommended use of thiazides to reduce occurrence of nephrolithiasis in the setting of hypercalciuria in patients with Dent disease (21)
Consideration for use of cyclosporine and RAAS blockade for the management of nephrotic syndrome in patients FSGS/SRNS due to WT1 (42)
Consideration for immunosuppression with rapamycin in a transplant recipient identified to be at risk for a hereditary cancer syndrome (43)
Avoidance of tacrolimus and corticosteroids post-transplant in patients with renal cysts and diabetes syndrome (HNF1B) to minimize risk of developing diabetes (25)
Consideration for RAAS blockade in males with X-linked Alport syndrome even before onset of proteinuria (44)
Aggressive BP control in early ADPKD can slow GFR loss (45)
For lipoprotein glomerulopathy (APOE), management of proteinuria with fenofibrates [either alone or in conjunction with other lipid lowering agents (46)] should be considered
Somatostatin therapy may be considered in patients with severe polycystic liver disease due to ADPKD (47)
Inform prognosisLoss-of-function variants associated with early onset of kidney failure, hearing loss, and ocular abnormalities in males and females with X-linked Alport syndrome (48,49)
Most patients with branchio-oto-renal syndrome (e.g., EYA1, SALL1, etc.) have hearing loss, which may be progressive (50)
There is a higher risk for antiglomerular basement membrane disease post-transplantation among patients with Alport syndrome due to a large deletion in the COL4A5 gene (26)
Initiate referral for subspecialty careIndividuals with Alport syndrome should be referred for audiometry, ophthalmologic review, retinal imaging, and, possibly, retinal optical coherence tomography (26)
Renal cysts and diabetes syndrome (HNF1B) patients should undergo imaging to screen for chromophobe renal cell carcinoma (51)
Guide familial testingCascade testing should be performed in at risk family members of an individual with X-linked Alport syndrome (26)
Preimplantation genetic diagnostics should be included in the discussion of reproductive choices among patients with ADPKD (52)
Assist with donor selectionMothers of affected males with Alport syndrome are discouraged from kidney donation because of their own increased risk of kidney failure and hypertension, and predonation biopsy should be mandatory to accurately determine the extent of damage and further discourage donation if kidney damage is severe (44)
Patients with renal cysts and diabetes syndrome (HNF1B) should be considered for simultaneous pancreatic and kidney transplantation (53)
Surveillance in patients with secondary findingsAvoidance of medications that prolong the QT interval and/or deplete serum magnesium and potassium levels (e.g., verapamil, loop diuretics, etc.) in patients with arrhythmogenic hereditary syndromes (e.g., SCN5A, etc.) who may be at increased risk for sudden death (23)
  • RAAS, renin–angiotensin–aldosterone system; FSGS/SRNS, focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome; ADPKD, autosomal dominant polycystic kidney disease.