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1. Patients with chronic nephropathies
2. Patients with acute nephropathy
3. Patients with nephrectomy
4. Candidate Patients to major surgery
5. Patients with decompensated heart failure undergoing either medical or surgical therapy
6. Acute critically ill patients (e.g sepsis, post-operative)
7. Patients with hypertension
8. Patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation.
9. Long-term surviving patients who received bone marrow transplantation.

genetic polymorphisms

Chiara Livia Lanzani, prof

Laura Zagato, biologist

Chiara Lanzani, MD

This study evaluates the role of genetic in the development and progression of different nephropaties with particular attention to:

* AKI
* CKD
* Hypertension
* ADPKD
* CKD-MBD
* Patients with decompensated heart failure undergoing either medical or surgery therapy
* Patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation
* glomerular diseases

Background: In the past ten years there's been a progressive increase in the prevalence of CKD and consequently in the number of dialysed patients (\~4% per year) in Italy. This is probably due to the increasingly ageing population and incidence of CV disease (cf. Lombardy Register). To date, diabetes and CV disease are the most common cause of end-stage renal disease (ESRD) requiring RRT. Nonetheless, intrinsic renal diseases still remain an important cause of CKD. In the past few years, various environmental factors have been identified that affect the clinical progression of kidney disease: blood pressure control, lipid and glycemic profile (expecially in the setting of diabetic nephropaty), uric acid level and acid-base homeostasis. Recently, there have been found some genes responsible for monogenic hereditary diseases such as ADPKD (PKD1 e PKD2) and Alport syndrome (COL4A3/COL4A4/COL4A5). It is known that there's an important phenotypic heterogeneity among different patients with the same disease even in the same family because of incomplete penetrance \[5\]. Furthermore, it is well known that familiarity overbear all other risk factors in predicting the development of hypertension and its progression toward CKD. Many scientific findings show the link between some genetic polymorphisms (e.g ACE, adducin) and disease severity or development of various complications. There is now, increasingly scientific evidence that genetic palys an important role even in the development and progression of multifactorial renal disease with both protective or promoting possible pathways. Thus, It would seem that interactions between environmental and genetic factors are responsible for disease phenotypic heterogeneity and its progression.

Aim of the study:

* Extend the knowledge on genetic modifiers involved in disease progression to better classify patients in homogeneous groups based on aetiology and concomitant risk factors. According to the underlying pathology, patients will be assessed either alone or with their family to evaluate the phenotypic heterogeneity.
* Evaluate the role of drugs that targets genetic or environmental factors.
* Assess the role of gentic background in the development of CV complications in CKD patients undergoing dyalisis.
* Assess the role of immature progenitor cells in the progression of kidney disease.
* Evaluate the role of endogenous Ouabain to identify at increased risk for AKI: 1) Postoperative patients. 2) patients with decompensated heart failure undergoing surgery or PCI. 3) patients with severe hypovolemic shock due to either cardiologic causes (e.g AMI) or from other causes (e.g sepsis, hypertensive crisis) 4) patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation.
* Identify the presence of genetic modifiers influencing the development and progression of CKD.
* Evaluate the role of genetic polymorphism in the transition from hypertension to kidney disease.
* Assess the role of salt intake in BP control and CKD progression either alone or in the presence of genetic modifiers.
* Evaluate the role of protein intake restriction in CKD progression eitehr alone or in the presence of genetic modifiers.
* Identify cortical bone lesions in CKD
* Assess the role of genetic, nutritional and biochemical factors involved in the cortical bone development
* Evaluate the role of genetic in the development of hypertension in patients who received allogenic bone marrow transplantation.

The genetic polymorphisms that will be considered, based on current knowledge are:

* Alpha, beta, gamma Adducin (ADD1, ADD2, ADD3),
* Renin Angiotensin System (RAAS),
* Glomerular proteins: nephrine, podocin, cadherin.
* Renal tubular transport systems (Na-Cl cotransport, Na channel, lithium, Cl channel, K channel, Ca channel, Amino Acids, specialized tubular transporters ouabain, drugs, digoxin, aquaporins, ANP, BNP).
* Genes linked to the metabolism and function of endogenous ouabain (eg LSS) and Klotho (eg KL).
* Polycystin 1, polycystin 2 (PKD1 and PKD2), uromodulline, S. di Alport (COL4A3/COL4A4/COL4A5)

For the study of any further genetic polymorphisms, additional amendments to this research protocol will be formulated.

Genetics in the Progression of Nephropathies

The Genetic Contribution to Progression of Kidney Disease

Ospedale San Raffaele

Clinical Assistant

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Genetics in the Progression of Nephropathies	NCT06416761	AKI CKD Ckd-Mbd CKD (Chronic Ki... ADPKD Hypertension Hematologic Mal... Bone Marrow Tra...	genetic polymor...	18 Years -	Ospedale San Raffaele
Genetics in the Progression of Nephropathies	NCT06416761	AKI CKD Ckd-Mbd CKD (Chronic Ki... ADPKD Hypertension Hematologic Mal... Bone Marrow Tra...	genetic polymor...	18 Years -	Ospedale San Raffaele

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