Autosomal dominant polycystic kidney disease

File:Polycystic kidney.jpg

polycystic kidney, external surface with multiple cysts.

File:Kiney with multiple cysts, some with old and more recent haemorrhage.jpg

Cut surface of kidney showing multiple cysts with old and more recent haemorrhage.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited human disorders and the most common hereditary kidney disease.<ref name="TP-150518-E20">Template:Cite journal</ref><ref>Template:Cite web</ref> It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes.<ref name="TP-150518-E20" /> It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias.<ref name="TP-150518-E20" /><ref name="Dalgaard_1957">Template:Cite journal</ref><ref name=torres>Template:Cite journal</ref> Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation.<ref name="TP-150518-E20" /><ref name="grantham">Template:Cite journal; Reprinted in Template:Cite journal</ref> ADPKD is estimated to affect at least one in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale.<ref name="TP-150514-001">Template:Cite journal</ref><ref name="TP-150518-E18">Template:Cite journal</ref><ref name="TP-150514-003">Template:Cite journal</ref><ref name="TP-150514-004">Template:Cite journal</ref><ref name="TP-150514-005">Template:Cite journal</ref>

Signs and symptoms

ADPKD can result in a wide variety of clinical symptoms. Symptoms may be caused directly by a cyst growing or bursting, or indirectly due to problems with other physiological functions. Most symptoms occur in the around 40 years of age but some clinical symptoms can occur decades prior to the development of over kidney disease, with some symptoms symptoms presenting as early as childhood.<ref name=":0">Template:Cite journal</ref><ref name=":1">Template:Cite journal</ref>

Primary Symptoms Include:<ref name=":1" />

• Early onset hypertension
• Blood in urine
• Abdominal, flank or back pain
• Masses in the abdomen or flank
• Decrease in renal function

Among the most common symptoms associated with is early onset hypertension. Early onset hypertension is present in 50%-70% percent of individuals with ADPKD.<ref name=":0" /> Hypertension can even develop before the decline in kidney function markers like GFR (glomerular filtration rates).<ref name=":0" />

The presence of ADPKD is associated with the a number of extra-renal symptoms including the development of cysts in organs outside of the kidney. Polycystic liver disease is a is often found in adults with ADPKD and can be present in greater than 90% of individuals with ADPKD over 35 years old.<ref name=":2">Template:Cite journal</ref> Polycystic liver disease develops more often in females with ADPKD than males, with risk factors including and exposure to non-endogenous sources of estrogen and multiple gestations. Individuals with polycystic liver disease due to ADPKD can also experience gastrointestinal symptoms related to presences of cysts in the liver such as early discomfort, fullness and gastro-esophageal reflux. In rare cases portal hypertension with secondary ascites and pleural effusion can also occur.

Individuals with the ADPKD are also at increased risk for the development of risk of intracranial aneurysms. The risk of intracranial aneurysms is estimated to be four times higher in people with ADPKD when compared to the general population and as a result screening with magnetic resonance angiography for high-risk populations.<ref name=":2" />

Additionally, symptoms such as a abdominal fullness, abdominal excessive urination, and reoccurring urinary tract infections (occurring more frequently in women than in men), kidney stones, bladder infection are also associated with ADPKD.<ref name=":0" />

ADPKD can also result in a wide array of symptoms beyond the kidneys resulting in the following symptoms:<ref name=":0" /><ref name=":2" />

• Neurological: Arachnoid cysts, intracranial hemorrhage.
• Cardiovascular: Pericardial effusion, mitral valve prolapse, bicuspid aortic valve
• Endocrine: Pancreatic cysts
• Gastrointestinal: Polycystic liver disease, diverticulosis
• Pulmonary: Bronchiectasis
• Reproductive: Male infertility, seminal vesicle cysts, ovarian cysts

Among the clinical presentation are:Template:Citation needed

• Acute loin pain
• Blood in the urine
• Ballotable kidneys
• Subarachnoid hemorrhage (berry aneurysm)
• Hypertension
• Associated liver cysts
• Uremia due to kidney failure
• Anemia due to chronic kidney disease
• Increase RBC or erythropoietin secretion

Signs and symptoms of ADPKD often develop between 30 and 40 years of age.<ref>Template:Cite web</ref>

Genetics

ADPKD is genetically heterogeneous with two genes identified: PKD1 (chromosome region 16p13.3; around 85% cases) <ref>Template:Cite journal</ref> and PKD2 (4q21; around 15% cases).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="TP-150518-E20" /> Several genetic mechanisms probably contribute to the phenotypic expression of the disease.<ref name="TP-150518-E20" /> Although evidence exists for a two-hit mechanism (germline and somatic inactivation of two PKD alleles) explaining the focal development of renal and hepatic cysts,<ref name="TP-150518-E22">Template:Cite journal</ref><ref name="TP-150518-E23">Template:Cite journal</ref> haploinsufficiency is more likely to account for the vascular manifestations of the disease.<ref name="TP-150518-E24">Template:Cite journal</ref><ref name="TP-150518-E25">Template:Cite journal</ref> Additionally, new mouse models homozygous for PKD1 hypomorphic alleles 22 and 23 and the demonstration of increased renal epithelial cell proliferation in PKD2 +/− mice suggest that mechanisms other than the two-hit hypothesis also contribute to the cystic phenotype.<ref name="TP-150518-E20" />

Large interfamilial and intrafamilial variability occurs in ADPKD.<ref name="TP-150518-E20" /> Most individuals with PKD1 mutations have kidney failure by age 70 years, whereas more than 50% of individuals with PKD2 mutations have adequate renal function at that age (mean age of onset of end-stage renal disease: 54·3 years with PKD1; 74·0 years with PKD2).<ref name="TP-150518-E26">Template:Cite journal</ref>

The significant intrafamilial variability observed in the severity of renal and extrarenal manifestations points to genetic and environmental modifying factors that may influence the outcome of ADPKD, and results of an analysis of the variability in renal function between monozygotic twins and siblings support the role of genetic modifiers in this disease.<ref name="TP-150518-E20" /><ref name="TP-150518-E27">Template:Cite journal</ref> It is estimated that 43–78% of the variance in age to ESRD could be due to heritable modifying factors,<ref name="TP-150518-E28">Template:Cite journal</ref><ref name="TP-150518-E29">Template:Cite journal</ref> with parents as likely as children to show more severe disease in studies of parent-child pairs.<ref name="TP-150518-E20" /><ref name="TP-150518-E30">Template:Cite journal</ref>

Pathophysiology

In many patients with ADPKD, kidney dysfunction is not clinically apparent until 30 or 40 years of life.<ref name="grantham"/> However, an increasing body of evidence suggests the formation of renal cysts starts in utero.<ref name="TP-150518-E31">Template:Cite journal</ref> Cysts initially form as small dilations in renal tubules, which then expand to form fluid-filled cavities of different sizes.<ref name="TP-150518-E31" /> Factors suggested to lead to cystogenesis include a germline mutation in one of the polycystin gene alleles, a somatic second hit that leads to the loss of the normal allele, and a third hit, which can be a renal insult that triggers cell proliferation, and an injury response.<ref>Template:Cite journal</ref> Due to numerous similarities between the pathophysiology of ADPKD and the pathophysiology of the renal response to injury, ADPKD has been described as a state of aberrant and persistent activation of renal injury response pathways.<ref>Template:Cite journal</ref> In the progression of the disease, continued dilation of the tubules through increased cell proliferation, fluid secretion, and separation from the parental tubule lead to the formation of cysts.<ref name="TP-150518-E32">Template:Cite journal</ref><ref name="TP-150518-E37">Template:Cite journal</ref>

ADPKD, together with many other diseases that present with renal cysts, can be classified into a family of diseases known as ciliopathies.<ref name="TP-150518-E33">Template:Cite journal</ref> Epithelial cells of the renal tubules, including all the segments of the nephron and the collecting ducts (with the exception of intercalated cells) show the presence of a single primary apical cilium.<ref name="TP-150518-E34">Template:Cite journal</ref> Polycystin-1, the protein encoded by the PKD1 gene, is present on these cilia and is thought to sense the flow with its large extracellular domains, activating the calcium channels associated with polycystin-2, the product of gene PKD2,<ref name="TP-150518-E35">Template:Cite journal</ref> as a result of the genetic setting of ADPKD as explained in the genetics sub-section above.

Epithelial cell proliferation and fluid secretion that lead to cystogenesis are two hallmark features in ADPKD.<ref name="TP-150518-E36">Template:Cite journal</ref> During the early stages of cystogenesis, cysts are attached to their parental renal tubules and a derivative of the glomerular filtrate enters the cysts.<ref name="TP-150518-E31" /> Once these cysts expand to approximately 2 mm in diameter, the cyst closes off from its parental tubule and after that fluid can only enter the cysts through transepithelial secretion, which in turn is suggested to increase due to secondary effects from an increased intracellular concentration of cyclic AMP (cAMP).<ref name="TP-150518-E31" />

Clinically, the insidious increase in the number and size of renal cysts translates as a progressive increment in kidney volume.<ref name="TP-150518-E20" /><ref name="TP-150518-E31" /> Studies led by Mayo Clinic professionals established that the total kidney volume (TKV) in a large cohort of ADPKD patients was 1060 ± 642ml with a mean increase of 204ml over three years, or 5.27% per year in the natural course of the disease, among other important, novel findings that were extensively studied for the first time.<ref name="TP-150515-017">Template:Cite journal</ref>

File:PKD1PKD2 en.png

Illustration of PKD1 and PKD2 proteins at the cell membrane

Diagnosis

Usually, the diagnosis of ADPKD is initially performed by renal imaging using ultrasound, CT scan, or MRI.<ref name="TP-150519-E40">Template:Cite journal</ref> However, molecular diagnostics can be necessary in the following situations: 1- when a definite diagnosis is required in young individuals, such as a potential living related donor in an affected family with equivocal imaging data;<ref name="TP-150519-E40" /> 2- in patients with a negative family history of ADPKD, because of potential phenotypic overlap with several other kidney cystic diseases;<ref name="TP-150519-E40" /> 3- in families affected by early-onset polycystic kidney disease, since in this cases hypomorphic alleles and/or oligogenic inheritance can be involved;<ref name="TP-150519-E40" /><ref name="TP-150519-E41">Template:Cite journal</ref> and 4- in patients requesting genetic counseling, especially in couples wishing a pre-implantation genetic diagnosis.<ref name="TP-150519-E40" /><ref name="TP-150519-E42">Template:Cite journal</ref>

The findings of large echogenic kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD are diagnostic. In the absence of a family history of ADPKD, the presence of bilateral renal enlargement and cysts, with or without the presence of hepatic cysts, and the absence of other manifestations suggestive of a different renal cystic disease provide presumptively, but not definite, evidence for the diagnosis. In some cases, intracranial aneurysms can be an associated sign of ADPKD, and screening can be recommended for patients with a family history of intracranial aneurysm.<ref name="TP-150818-01">Template:Cite journal</ref>

Molecular genetic testing by linkage analysis or direct mutation screening is clinically available; however, genetic heterogeneity is a significant complication to molecular genetic testing. Sometimes, a relatively large number of affected family members need to be tested in order to establish which one of the two possible genes is responsible within each family. The large size and complexity of PKD1 and PKD2 genes, as well as marked allelic heterogeneity, present obstacles to molecular testing by direct DNA analysis. The sensitivity of testing is nearly 100% for all patients with ADPKD who are age 30 years or older and for younger patients with PKD1 mutations; these criteria are only 67% sensitive for patients with PKD2 mutations who are younger than age 30.Template:Citation needed

• Adult polycystic kidney
  Adult polycystic kidney
• Diagram of autosomal dominant polycystic disease with a normal kidney inset for comparison
  Diagram of autosomal dominant polycystic disease with a normal kidney inset for comparison
• Abdominal CT scan of an adult with autosomal dominant polycystic kidney disease: Extensive cyst formation is seen over both kidneys, with a few cysts in the liver, as well. (Coronal plane)
  Abdominal CT scan of an adult with autosomal dominant polycystic kidney disease: Extensive cyst formation is seen over both kidneys, with a few cysts in the liver, as well. (Coronal plane)

Treatment

Currently, the only pharmacological treatment available for ADPKD consists in reducing the speed in gain of total kidney volume (TKV) with vasopressin receptor 2 (V2) antagonists (i.e. tolvaptan).<ref>Template:Cite web</ref> Tolvaptan treatment does not halt or reverse disease progression and patients still progress towards renal failure. Palliative treatment modalities involve symptomatic medications (nonopioid and opioid analgesics) for abdominal/retroperitoneal pain. Options for analgesic-resistant pain include simple or complex surgical procedures (i.e. renal cyst aspiration, cyst decortication, renal denervation and nephrectomy), which can result in complications inherent to surgery.Template:Citation needed Recent research suggests that ketogenic dietary interventions beneficially affect the progression and symptoms in individuals with ADPKD.<ref name = "Strubl_2021">Template:Cite journal</ref> Mild weight loss favorably affects pain<ref>Template:Cite journal</ref> indicating the benefit of dietary and lifestyle changes.

Aquaretic medication

In 2014, Japan was the first country in the world to approve a pharmacological treatment for ADPKD<ref name="TP-150515-017" /> followed by Canada and Europe, which approved the drug tolvaptan for ADPKD patients in the beginning of 2015. The USA FDA approved the use of tolvaptan in the treatment of ADPKD in 2018.<ref>Template:Cite web</ref> Tolvaptan, an aquaretic drug, is a vasopressin receptor 2 (V2) antagonist.<ref name="TP-150514-004" /> Pre-clinical studies had suggested that the molecule cAMP could be involved in the enlargement of ADPKD cysts,<ref name="Hanaoka and Guggino">Template:Cite journal</ref> and studies on rodents confirmed the role of vasopressin in increasing the levels of cAMP in the kidney, which laid the basis for the conduction of clinical studies.<ref name="TP-150519-E44">Template:Cite journal</ref> Because data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) led by Mayo Clinic showed that total kidney volume (TKV) predicted the risk of developing chronic kidney disease in patients with ADPKD,<ref name="TP-150515-017" /><ref name="TP-150519-E39">Template:Cite journal</ref> the TEMPO 3:4 trial, which enrolled patients from 129 sites worldwide from 2007 to 2009, evaluated TKV as a primary end-point to test the efficacy of tolvaptan in ADPKD patients.<ref name="TP-150514-004" /><ref name="TP-150514-005" /> That study showed a significant decrease in the ratio of TKV increase and deterring of renal function decline in ADPKD patients after treatment with tolvaptan;<ref name="TP-150514-004" /><ref name="TP-150515-007">Template:Cite journal</ref> however, because laboratory test results regarding liver function appeared elevated in a percentage of patients enrolled in that study, the approval of the drug was either delayed by regulatory agencies or, as in case of the US, altogether denied.<ref name="TP-150514-005" /><ref name="TP-150515-012">Template:Cite journal</ref>

Dietary and lifestyle interventions

Research using ADPKD mouse models showed that mild food restriction strongly improved disease progression.<ref>Template:Cite journal</ref> The mechanism was shown to involve the metabolic state of ketosis, and beneficial effects could be produced by time-restricted feeding, acute fasting, a ketogenic diet, or by supplementation with the ketone beta-hydroxybutyrate in mouse, rat and cat models of ADPKD.<ref name="rat model">Template:Cite journal</ref><ref name="ketosis">Template:Cite journal</ref> A ketogenic diet regimen not only halted further disease progression but led to partial reversal of renal cystic disease in a rat model.<ref name="ketosis"/> The metabolic state of ketosis may be beneficial in ADPKD because renal cyst cells in ADPKD have a metabolic defect similar to the Warburg effect in cancer that makes them highly dependent on glucose, and unable to metabolize fatty acids and ketones.<ref name="rat model" /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Consistent with this, serum glucose levels positively correlate with faster disease progression in ADPKD patients.<ref>Template:Cite journal</ref> Also, individuals with ADPKD and type 2 diabetes have significantly larger total kidney volume (TKV) than those with ADPKD alone,<ref>Template:Cite journal</ref> and overweight or obesity associate with faster progression in early-stage ADPKD.<ref>Template:Cite journal</ref> A retrospective case series study showed that ADPKD disease symptoms - including pain, hypertension and renal function - improved among 131 patients who implemented ketogenic diets for an average duration of 6 months.<ref name = "Strubl_2021" />

Dietary intake of sodium is associated with worse renal function decline in ADPKD,<ref>Template:Cite journal</ref> and limiting sodium intake is generally recommended to patients. Dietary protein intake was not found to correlate with ADPKD progression.<ref>Template:Cite journal</ref>

Increased water intake is thought to be beneficial in ADPKD and is generally recommended.<ref name = "Torres_2019">Template:Cite journal</ref><ref>Template:Cite journal</ref> The underlying beneficial mechanism of increased water intake may be related to effects on the vasopressin V2 receptor or may be due to the suppression of harmful micro-crystal formation in renal tubules by dilution of solutes such as calcium oxalate, calcium phosphate and uric acid.<ref name = "Torres_2019" /><ref>Template:Cite journal</ref>

Dietary intake of oxalate or inorganic phosphate has been shown to accelerate PKD disease progression in several rodent models.<ref name = "Torres_2019" /> Low levels or urinary citrate – a natural antagonist of the formation of harmful crystals in kidney tubules – have been shown to associate with worse disease progression in ADPKD patients.<ref name = "Torres_2019" />

Analgesic medication

Chronic pain in patients with ADPKD is often refractory to conservative, noninvasive treatments, but nonopioid analgesics and conservative interventions can be first used before opioid analgesics are considered; if pain continues, then surgical interventions can target renal or hepatic cysts to directly address the cause of pain, with surgical options including renal cyst decortication, renal denervation, and nephrectomy.<ref name="TP-150515-E02">Template:Cite journal</ref>

Renal cyst aspiration

Aspiration with ethanol sclerotherapy can be performed for the treatment of symptomatic simple renal cysts, but can be impractical in advanced patients with multiple cysts.<ref name="TP-150515-E03">Template:Cite journal</ref> The procedure itself consists in the percutaneous insertion of a needle into the identified cyst, under ultrasound guidance, with subsequent draining the contained liquid; the sclerotherapy is used to avoid liquid reaccumulation that can occur in the cyst, which can result in symptom recurrence.<ref name="TP-150515-E03" /><ref name="TP-150515-E07">Template:Cite journal</ref>

Laparoscopic cyst decortication

Laparoscopic cyst decortication (also referred to as marsupialization) consists in the removal of one or more kidney cysts through laparoscopic surgery, during which cysts are punctured, and the outer wall of the larger cysts is excised with care not to incise the renal parenchyma.<ref name="TP-150515-E04">Template:Cite journal</ref><ref name="TP-150515-E05">Template:Cite journal</ref> This procedure can be useful for pain relief in patients with ADPKD, and is usually indicated after earlier cyst aspiration has confirmed that the cyst to be decorticated is responsible for pain.<ref name="TP-150515-E05" /> Nonrandomised controlled trials conducted in the '90s showed that patients with symptomatic simple renal cysts who had recurrence of symptoms after initial response to simple aspiration could be safely submitted to cyst decortication, with a mean pain-free life between 17 and 24 months after surgery.<ref name="TP-150515-E04" /><ref name="TP-150515-E06">Template:Cite journal</ref> Laparoscopic decortication presents a 5% recurrence rate of renal cysts compared to an 82% recurrence rate obtained with sclerotherapy.<ref name="TP-150515-E07" />

Neurolysis

A novel treatment of specifically the chronic pain experienced by many with ADPKD is Celiac plexus neurolysis.<ref name="pmid28159317">Template:Cite journal</ref><ref>Template:Cite journal</ref> This involves the chemical ablation of the celiac plexus, to cause a temporary degeneration of targeted nerve fibers. When the nerve fibers degenerate, it causes an interruption in the transmission of nerve signals. This treatment, when successful, provides significant pain relief for a period ranging from a few days to over a year. The procedure may be repeated when the affected nerves have healed and the pain returns.<ref>Template:Cite journal</ref>

Nephrectomy

Many ADPKD patients experience symptomatic sequelae in consequence of the disease, such as cyst hemorrhage, flank pain, recurrent infections, nephrolithiasis, and symptoms of mass effect (i.e., early satiety, nausea and vomiting, and abdominal discomfort), from their enlarged kidneys.<ref name="TP-150518-E08">Template:Cite journal</ref><ref name="TP-150518-E09">Template:Cite journal</ref><ref name="TP-150518-E13">Template:Cite journal</ref> In such cases, nephrectomy can be required due to intractable symptoms or when in the course of preparing for kidney transplantation, the native kidneys are found to impinge upon the true pelvis and preclude the placement of a donor allograft.<ref name="TP-150518-E09" /><ref name="TP-150518-E13" /><ref name="TP-150518-E10">Template:Cite journal</ref><ref name="TP-150518-E11">Template:Cite journal</ref> Additionally, native nephrectomy may be undertaken in the presence of suspected malignancy, as renal cell carcinoma (RCC) is two to three times more likely in the ADPKD population in end-stage kidney disease (ESKD) than in the ESKD patients without ADPKD.<ref name="TP-150518-E13" /><ref name="TP-150518-E12">Template:Cite journal</ref> Although the indications for nephrectomy in ADPKD may be related to kidney size, the decision to proceed with native nephrectomy is often undertaken on an individual basis, without specific reference to kidney size measurements.<ref name="TP-150518-E13" />

Dialysis

Two modalities of dialysis can be used in the treatment of ADPKD patients: peritoneal dialysis and hemodialysis.<ref name="TP-150518-E14">Template:Cite journal</ref> Epidemiological data shows that ADPKD affects 5–13.4% of patients undergoing hemodialysis in Europe and in the United States,<ref name="TP-150518-E15">Template:Cite journal</ref><ref name="TP-150518-E16">Template:Cite journal</ref><ref name="TP-150518-E17">Template:Cite journal</ref> and about 3% in Japan.<ref name="TP-150518-E18"/> Peritoneal dialysis has usually been contra-indicated in ADPKD patients with large kidney and liver volumes, due to expected physical difficulties in the procedure and possible complications;<ref name="TP-150518-E14" /><ref name="TP-150518-E19">Template:Cite journal</ref> however, no difference is seen in long-term morbidity between hemodialysis and peritoneal dialysis in ADPKD.<ref name="TP-150518-E14" />

Kidney transplant

Kidney transplantation is accepted as the preferred treatment for ADPKD patients with ESRD.<ref name="TP-150518-E20" /> Among American patients on the kidney-transplant waiting list (as of December 2011), 7256 (8.4%) were listed due to cystic kidney disease and of the 16,055 renal transplants performed in 2011, 2057 (12.8%) were done for patients with cystic kidney disease, with 1,189 from deceased donors and 868 from living donors.<ref name="TP-150518-E21">Template:Cite journal</ref>

Novel Therapies

There are several novel therapies currently underway aimed at slowing the progression of disease in APKD. Alternative therapeutic options water therapy, use of lipid lowering agents, antiproliferative analogues and synthetic peptides.<ref name=":2" />

Water Therapy

Increased water intake downregulates vasopressin activity As a result water therapy has been explored as a potential therapeutic intervention for individuals with ADPKD, however studies have examining its role in ADPKD advancement remain unclear.<ref name=":2" />

HMG-CoA reductase inhibitors

The progression of ADPKD leads to decline in kidney function, with a marked decreased in glomerular filtration rate. As a result, treatment with statins is recommended in accordance with current guidelines for managing chronic kidney disease. The effect of statins on slowing ADPKD are inconclusive, with some trials showing a decrease in total kidney volume, while others showed no benefit on either total kidney volume or glomerular filtration rate.<ref name=":2" />

Somatostatin analogs

Somatostatin are artificial peptides designed to mimic the function of endogenous hormone that has many regulatory functions within the body including restraining cell proliferation. Small phase 2 studies have shown that somatostatin analogues are effective at reducing the rate of total kidney volume growth and preserving glomerular filtration rate.<ref name=":2" /> The use of somatostatin analogues may be restricted due to their side effects, which commonly include gastrointestinal issues such as diarrhea, abdominal discomfort, and gas, as well as conditions like gallstones and elevated blood sugar.

Anti-proliferative agents

Proliferation of epithelial cells lining cyst resulting in cyst expansion and contributing to disease progression. As a result of this mechanism, antiproliferative agents such as tyrosine kinase inhibitor bosutinib. However, results in clinical trails have shown mixed results, with studies showing a decrease in total kidney volume. <ref name=":2" /><ref>Template:Cite journal</ref>

Prognosis

In ADPKD patients, gradual cyst development and expansion result in kidney enlargement, and during the course of the disease, glomerular filtration rate remains normal for decades before kidney function starts to progressively deteriorate, making early prediction of renal outcome difficult.<ref name="TP-150519-E38">Template:Cite journal</ref> The CRISP study,<ref name="TP-150515-017" /><ref name="TP-150519-E39"/> mentioned in the treatment section above, contributed to build a strong rationale supporting the prognostic value of total kidney volume (TKV) in ADPKD; TKV (evaluated by MRI) increases steadily and a higher rate of kidney enlargement correlated with accelerated decline of GFR, while patient height-adjusted TKV (HtTKV) ≥600 ml/m predicts the development of stage 3 chronic kidney disease within 8 years.<ref name="TP-150519-E38" />

Besides TKV and HtTKV, the estimated glomerular filtration rate (eGFR) has also been tentatively used to predict the progression of ADPKD.<ref name="TP-150519-E38" /> After the analysis of CT or MRI scans of 590 patients with ADPKD treated at the Mayo Translational Polycystic Kidney Disease Center, Irazabal and colleagues developed an imaging-based classification system to predict the rate of eGFR decline in patients with ADPKD.<ref name="TP-150519-E38" /><ref name="TP-150519-E39"/> In this prognostic method, patients are divided into five subclasses of estimated kidney growth rates according to age-specific HtTKV ranges (1A, <1.5%; 1B, 1.5–3.0%; 1C, 3.0–4.5%; 1D, 4.5–6.0%; and 1E, >6.0%) as delineated in the CRISP study.<ref name="TP-150519-E38" /><ref name="TP-150519-E39" /> The decline in eGFR over the years following initial TKV measurement is significantly different between all five patient subclasses, with those in subclass 1E having the most rapid decline.<ref name="TP-150519-E38" /> Some of the most common causes of death in patients with ADPKD are various infections (25%), a ruptured berry aneurysm (15%), or coronary/hypertensive heart disease (40%).<ref>Template:Cite book</ref>

External links

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