Predictors of Autosomal Dominant Polycystic Kidney Disease Progression

Abstract

Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.

The PROPKD Score

“…(B) Significant differences in renal survival in patients from the three prognostic categories, as follows: low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of early progression to ESRD. Diet in Renal Disease formula, or the age at ESRD onset, which was defined according to the requirement for dialysis or transplantation, and factors that have been reported to influence renal survival, 20 such as BP, age at hypertension (defined as the age when the first antihypertensive therapy was administered), the previous occurrence of urologic events (gross hematuria, symptomatic cyst hemorrhage, cyst infections, and flank pain related to cysts), the number of births in women, and smoking status. According to the literature, the threshold of 35 years was chosen for all complications to categorize patients.…”

Tolvaptan in the treatment of autosomal dominant polycystic kidney disease: patient selection and special considerations

“…Although there is currently no standard definition of rapidly progressing ADPKD, clinicians must have the ability to correctly identify patients, who would benefit from treatment initiation, and also avoid treatment initiation in those patients in whom the risks linked to treatment outweigh the benefits. 12 Reimbursing criteria are supposed to correctly balance the patient selection to give a clear benefit to those patients who may have a fast progression and avoid risks in those whom treatment initiation will not change the course of the disease. These criteria, based on available evidence, should in theory be quite similar from one country to another.…”

“…Other biomarkers are worth mentioning: plasma copeptin, a surrogate for plasma AVP, 47 is another biomarker underlining the link between V2R signaling, Usom, and early ADPKD progression. Regarding urine, albuminuria, 48,49 monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), tumor necrosis factoralpha, and proteomic profile 12,50 have shown good correlations with disease severity and disease progression.…”

“…12,15 The main cellular events linked to cyst enlargement are cellular proliferation and intracystic fluid secretion. Several molecular pathways, including mTOR, Src, and cAMP, have been shown to modulate these elements within tubular epithelial cells and to reduce cystic growth.…”

Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease

“…[1][2][3] Total kidney volume in ADPKD is accurately measured with the use of magnetic resonance imaging (MRI). [4][5][6] Hypertension occurs early 6,7 and is associated with progression to end-stage renal disease (ESRD) and death from cardiovascular causes in patients with ADPKD. 8,9 Immunohistologic studies 10,11 and clinical studies 12,13 support a central role of the reninangiotensin-aldosterone system (RAAS) in the pathogenesis of hypertension in patients with ADPKD.…”