Renasight™ Case Studies
Discover how Renasight™ delivers meaningful utility and is revolutionizing patient management through genetic insights. Explore real-world case examples demonstrating improved diagnostics, personalized treatment plans, and enhanced patient care.
Case Study 1: Family History & Patients of African Ancestry- APOL1
Clinical History and Demographics
Patient history
- Recent lab work showed decreased kidney function prompting a nephrology referral for further evaluation
- Urinalysis showed proteinuria that will be monitored
- Diagnosed with CKD stage 2-3
- Patient has a sibling who is on dialysis
- No other family history of renal disease
- Children who have no known kidney concerns
Rationale for genetic test
- Clarify etiology of proteinuria/CKD
- First degree relative with CKD
- Variability in severity within the family
- Assess appropriateness of therapies
- Counsel on likelihood of disease progression
Renasight™ Result – APOL1
APOL1-Mediated Kidney Disease (AMKD)
Inheritance : Autosomal Recessive/ Complex
Incidence : 13% of African-Americans carry two risk alleles.
What is it : A risk factor to develop focal segmental glomerulosclerosis and kidney failure
- Individuals with two APOL1 risk alleles have a 7- to 30-fold increased risk of developing kidney disease.
- Lifetime risk of ESRD for high risk individuals may be up to 15%.
APOL1-Mediated Kidney Disease (AMKD): Clinical Utility
Identifies etiologic factor of proteinuria/CKD
Can predict accelerated progression of CKD
APOL1 status can inform need for future biopsy
Informs recurrence risk should patient require transplantation
Consider clinical trial opportunities
Enables patient to benefit from advances in targeted therapies to delay disease progression
Informs risk to relatives
Should transplant be needed, APOL1 testing in living related candidates can be considered
Case Study 2: FSGS – Alport syndrome
Clinical Diagnoses with Genetic Origins
Patient history
- Male patient found to have hematuria at a routine visit with his primary physician as a young adult and referred to nephrology
- Persistent proteinuria developed leading to a renal biopsy that showed FSGS
- CKD stage 4 in his 40s
- Maternal grandfather and a great aunt with history of ESRD
Rationale for genetic test
- Clarify etiology of proteinuria and FSGS
- Maternal family history of disease
- Assess appropriateness of therapies
- Counsel on likelihood of disease progression
Renasight™ Result – COL4A5
X-linked Alport Syndrome: Clinical Utility
Identified cause for proteinuria, CKD and FSGS
Informed risk for progression to ESRD
Identified risk for hearing and vision deficits
Informed on decision to biopsy
Low recurrence risk should patient require transplantation
Begin treatment with RAAS blockade as guidelines advise
Avoided immunosuppression trials
Identification of at-risk relatives
Informed family planning/ reproductive testing options
- Genetic testing is more sensitive and specific than kidney biopsy and is recommended as the gold standard
- When Alport syndrome is suspected, NGS can identify up to 95% of pathogenic COL4A- variants
- Genetic testing is recommended in patients with:
- First degree relative with a COL4A3-COL4A5 variant – this especially includes potential donors
- Persistent hematuria >6 months
- Persistent proteinuria, SRNS, or biopsy-proven FSGS
- Kidney failure without an obvious cause
- Familial IgA glomerulonephritis
Phenotypic spectrum of Alport syndrome
Case Study 3: Hypertension – UMOD
Unknown/Unclear Cause of CKD
Patient history
- CKD stage 4 attributed to hypertension and NSAID use
- History of gout
- Sibling with renal cysts; no known renal dysfunction
- Father had renal transplant in his 40s
- Another paternal family member had history of ESRD
Rationale for genetic test
- Clarify etiology of CKD
- Several relatives with CKD
- Intrafamilial variability in presentation of CKD
- Assess appropriateness of therapies
- Counsel on likelihood of disease progression
Renasight™ Result – UMOD
KDIGO Consensus Report on ADTKD
Autosomal Dominant Tubulointerstitial Kidney Disease.
Table 2 | Usual clinical findings in patients with ADTKD
- Autosomal dominant inheritance
- Progressive loss of kidney function
- Bland urinary sediment
- Absent-to-mild albuminuria/proteinuria
- No severe hypertension during early stages
- No drug exposure potentially causing tubulointerstitial nephritis
- Normal or small-sized kidneys on ultrasound
- Nocturia or enuresis in children (owing to loss of renal concentration ability)
Table 3 | Usual findings on renal history in patients with ADTKD
- Interstitial fibrosis
- Tubular atrophy
- Thickening and lamellation of tubular basement membranes
- Possibly tubular dilation (microcysts)
- Negative immunofluorescence for complement and immunoglobulins
"Genetic testing is currently the only way to definitively prove ADTKD and its respective subtypes, and exclude the disease in affected family members"
- UMOD gene accounts for 70% of ADTKD
- Usually inherited (de novo is rare)
- Hyperuricemia, low fractional urate excretion (<5%)
- Early gout for age
- Occasional renal cysts
- Average age of ESRD is 54 yrs (25-70 yrs)
- Intrafamilial variability
- Allopurinol or febuxostat treats gout and hyperuricemia
- No specific renal treatment BUT successful transplant from unaffected donor is considered a cure
UMOD-related disease: Clinical Utility
Reclassified etiology from HTN/NSAID to one originating from the UMOD gene
Explained the history of gout
Identify risk for progression to ESRD
Inform on decision to biopsy since cause was identified and histologic findings are often nonspecific
Renal transplant from unaffected donor is considered a cure
Identification of at-risk family members with a 50% recurrence risk
Definitive test for related, eligible donor candidates
Case Study 4: Transplant Candidate Informing Donor Eligibility
Transplant candidate with cystic disease
Patient history
- CKD stage 5, renal cysts, hypertension
- Diagnosed with ADPKD
- Family history unknown
Rationale for genetic test
- Clarify etiology of CKD
- Assess appropriateness of therapies
- Anticipate pre and post transplant course
Renasight™ Result – HNF1B
Phenotypic spectrum of HNF1B-related ADTKD
- Formerly referred to as Renal Cysts and Diabetes syndrome
- Most common known monogenic cause of developmental renal disease
- Strong intrafamilial variability
- Can manifest in prenatal period (agenesis/hypoplasia)
- Cystic disease in 73%
- Diabetes develops in ~50%
- Electrolyte abnormalities
- Hypomagnesemia, hyperuricemia (gout)
- 50% risk to children
HNF1B-related disease: Clinical Utility
Inform on treatment given nonclassic form of PKD
Identify risk for multiple extra-renal features
Increased risk of new-onset diabetes after transplant (NODAT), IS regimen that avoids tacrolimus and reduces corticosteroid exposure
Identification of at-risk family members given 50% risk of recurrence
Test available for eligible donor candidates in which intrafamilial variability is common