Autosomal dominant polycystic kidney disease: updated perspectives

Figures & data

Table 1 How autosomal dominant polycystic kidney disease affects the kidneys

1. Hypertension

2. Acute and chronic pain

3. Cyst and urinary tract infections

4. Hematuria

5. Kidney stones

6. Urine concentration defects

7. Loss of renal function

Note: Data from these studies.^6,65

Figure 1 Pathophysiology and genetics of autosomal dominant polycystic kidney disease showing the multiple abnormal signaling pathways.

Abbreviations: cAMP, cyclic adenosine monophosphate; MEK/MAPK, mitogen-activated protein kinase enzymes; mTOR, mammalian target of rapamycin; PC1, polystin-1 receptor, PC2, polycystin-2 receptor; PKA, protein kinase A, PDE1, phosphodiesterase isoform 1; PDE3, phosphodiesterase isoform 3.

Table 2 Unified ravine criteria for autosomal dominant polycystic kidney disease

Age	Number of cysts
15–39 years	At least 3 unilateral or bilateral kidney cysts
40–59 years	At least 2 cysts in each kidney
Above 60 years	At least 4 cysts in each kidney

Note: Data from Pei et al.¹⁴

Figure 2 Increase in kidney size and decrease in kidney function estimated by eGFR Correlated with age.

Table 3 Risk factors for rapid autosomal dominant polycystic kidney disease progression

1. PKD1 mutations (Truncating mutations has the worst outlook)

2. Age

3. Male gender

4. Early decrease in GFR

5. Early onset of hypertension

6. High total kidney volume (Mayo Classification 1C-1E)

7. Early onset or repeated episodes of gross hematuria

8. Women with hypertension, three or more pregnancies

9. Proteinuria, microalbuminuria and elevated serum copeptin levels

10. Overweight/Obesity

Note: Data from these studies.^43,78

Table 4 Therapies slowing the progression of autosomal dominant polycystic kidney disease (ARPKD)

Therapy	Mechanism of Action	Clinical Trial/Duration	Effect on eGFR (therapy vs placebo)	Effect on TKV Growth (therapy vs placebo)
Tolvaptan^Citation35	Vasopressin V2 receptor antagonist	TEMPO ¾/ 3 years	−2.61 vs −3.81 mg/mL per year (P<0.001)	2.8% vs 5.5% per year (P<0.001)
Octreotide^Citation90	Somatostatin analogue	ALADIN/3 years	−3.9 vs −5.0 mL/min/1.73 m2 in 3 years (P= NS)	46.2 mL vs 143.7 mL per year (P=0.03)
Lanreotide^Citation23	Somatostatin analogue	DIPAK/2.5 years	−3.53 vs −3.46 mL/min/1.73 m2 per year (P = 0.81)	4.15% vs 5.56% per year (P = 0.02)
Everolimus^Citation91	mTOR inhibitor	Walz et al./2 years	−8.9 vs −7.7 mL/min/1.73 m2 at 2 years (P=0.15)	102 mL vs 157 mL (P=0.02) at 1 year 230 mL vs 301 mL (P=0.06) at 2 years
Pravastatin^Citation76	Statin-related inhibition of G proteins	Cadnapaphornchai et al/2 years	Creatinine clearance: 126 vs 126 mL/min (P=0.98)	46% versus 68% per 2 years (P=0.03)
Metformin	AMPK activation, CFTR and mTOR suppression	NCT02656017/Started January 2016	Ongoing phase 2	Ongoing phase 2
Tesevatinib (ARPKD)	Tyrosine kinase inhibitor	NCT03096080/Started March 2017	Ongoing phase 1	Ongoing phase 1

Abbreviation: TKV, total kidney volume.

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