تشخیص

¨   Chronic Kidney Disease(CKD)

¨   Is when one suffer from gradual and usually permanent loss of kidney function over time. This happens gradually over time, usually month to years.

¨  KIDNEY FAILURE

¨   Occurs when the kidney partly or completely lose their ability to carry out normal function.

¨   DEFINITION: GFR < 15 ml / min / 1.73m2, with sign and symptoms of uremia or the need for dialysis / transplant for treatment of complications of decreased GFR that increase risks of mortality and morbidity.

¨   ESRF, is administrative term in the USA, for the payment of healthcare by the Medicare ESRF program.   

¨   1 – RENAL IMPAIRMENT. GFR = > 80ml, but loss of reserve function.

¨   2 – MILD RENAL INSUFFICIENCY. GFR = 50 – 80ml, renal mass is 25 – 50%.

¨   3 – MODERATE RENAL INSUFFICIENCY. GFR = 30 – 50ml, renal mass is 15 – 25%.

¨   4 – SEVER RENAL INSUFFICIENCY, GFR = 10 – 30ml, renal mass is 5 – 15%.

¨   5 – END-STAGE RENAL FAILURE. GFR < 10ml, renal mass<5%.

¨  CKD:

¨   Stages of chronic kidney disease:

       1 – kidney damage with normal GFR, ( > 90 ml ).

       2 – kidney damage with mildly decrease GFR, as

            ( 60 – 89 ml ).

       3 – moderate decrease in GFR, as ( 30 – 50 ml ).

       4 – sever decrease in GFR, ( 15 – 29 ml ).

       5 – kidney failure, GFR < 15 ml or on dialysis.

It is possible to have a GFR 60 -89ml/min/1.73m2 without kidney damage. In INFANT, VEGETRIAN DIET, UNILATERAL NEPHRECTOMY, VOLUME DEPLETION, HEART FAILURE.

¨  Cause of CKD:

¨   1 – Congenital abnormalities.

¨   2 – Hereditary condition.

¨   3 – Glomerulonephritis.

¨   4 – Multisystem disease.

¨   5 – Miscellaneous:

                                 -renal vascular disease,

                                              -kidney tumor,

                                              -drash syndrome,

                                              -others.

¨  Case presentation:    

¨   a 13 years-old girl presented with increasing fatigue, anorexia, weight loss, and sever pallority. She also had a history of polyuria, polydipsia, since infancy, and enuresis, nocturia. Her family history was unremarkable.

¨   Serum Creatinine was markedly elevated, and urinalysis showed a low SG, with mild proteinuria and glycosuria. US showed small echogenic kidneys with multiple small cortico- medullary cysts. 
 

¨  DIFFERENTIAL DIAGNOSIS

¨   1 – CYSTIC DISEASE: ARPCK.

                                                     ADPCK.

                                                     GCKD.

                                                     SIMPLE CYSTS.

                                                     DIFFUSE CYSTIC DYSPLASIA.

                                                     CONGENITAL SYNDROMES.

                                                     NPHP/MCKD COMPLEX.

                                                     CHRONIC PYELONEPHRITIS.

                                                     UT OBSTRUCTION.

                                                     OLIGOMEGANEPHRONIC DYSPLASIA.

                                                          MEDULLARY SPONGE KIDNEY
 

¨   Clinical presentation and evaluation of cystic disease

¨   Renal cystic disorders represent a heterogeneous group of diseases which may present in utero or be clinically silent well into adulthood.

¨   The age of presentation, family history, and other clinical signs and symptoms are essential in delineating specific disease entities.

¨   Cystic disorders include: ARPCK, ADPCK, GCKD, diffuse cystic dysplasia, simple cyst, MCD/JNPH, and ACKD(acquired).

¨   Cystic kidneys are an important component of several congenital syndrome.
 

¨  ARPCK: autosomal recessive PCK.

¨   This presentation of a neonate with oligohydramnios, respiratory distress, large echogenic kidneys, and HTN. Renal function is normal in in the neonatal period.

¨   Hepatic fibrosis is invariably present histologically, (abnormality are classically restricted to the liver and kidney, and occasionally multiple intracranial aneurysms in the adults).

¨   Detailed family history, US of the parents, and the presence of associated anomalies are more helpful in establishing the diagnosis 
 

¨  ADPCK: autosomal dominant PCK.

¨   The presentation is from neonate to adulthood.

¨   Symptoms include hematuria, HTN, flank pain, UTI and sterile pyuria.

¨   US demonstrates one or more macroscopic cysts.

¨   ADPCK is a systemic disease, with multiorgan system involvement. Intracranial aneurysms, mitral valve prolapse, liver and pancreatic cyst, ovarian cysts, intestinal diverticuli, and hernias may also develop.

¨   ADPCK is responsible for 8 – 10% of cases of ESRF in Europe.
 

¨  CONT:

¨   Glomerulocystic Kidney Disease: typically present in the neonatal period, with large echogenic kidneys and microscopic glomerular cysts.

¨   SIMPLE CYSTS: is age dependent, and occurring < 1% in children.

¨   DIFFUSE CYSTIC DYSPLASIA: occurs primarily as a sporadic condition, or as a part of multiple malformation syndromes. In the cysts is primitive  elements such as cartilage.

¨   Acquired Cystic Kidney Disease: occurs in ESRF, that are on dialysis. And kidney is enlarged.

¨  NPHP/MCKD complex:

¨   as a distinct clinicopathologic entity of inherited  diseases that lead to CRF, due to chronic sclerosing  TINephropathy. ( cystic formation, tubular atrophy, tubular basement membrane disintegration, interstitial fibrosis).

¨   NPHP is an aut. rec. disease with onset of ESRF in adolescence, and is the most frequent genetic cause of CRF in first two decades of life ( 10 – 20% of all cases ).

¨   MCKD is used for aut. dom. Variants with onset in adulthood.

¨     NPHP/MCKD, divided as INFANTILE, JUVENILE, and ADOLESCENT, forms.

¨   INFANTILE NPHP: NPHP2, in which ESRF, occurs within the first 3 years of life. It has enlarged kidneys and cortical micro cysts, absence of medullary cysts. Gene locus was localized to 9q22-q31. (is same as ARPCK).

¨   JUVENILE NPHP: NPHP1, a gene locus has been mapped to chromosome 2q12.3 (NPHP1). Some of patients has extra-renal manifestation.

¨   ADOLESCENT NPHP: NPHP3, has been localized to chromosome 3q21-q22.

¨   The disease genes for NPHP4 – 8 has been identified.

¨    The proteins for which they encoded are known, as the NEPHROCYSTINS, that localized at least in part to an organelle in the cell called the primary CILIA.  

¨  NPHP/MCKD complex:  clinical manifestation,

¨   This diseases characterized by the insidious onset of renal failure.

¨   In recessive NPHP, symptoms of polyuria, polydipsia, decrease urinary concentrating ability, 2^nd enuresis, are the earliest presenting symptoms in more than 80% of cases, and occur at 4 – 6 years of age.

¨   Starting to regularly drink at night at 6 – 10 years old.

¨   Pallor, weakness, and pruritus are common.

¨   Anemia and growth retardation occur latter and are usually pronounced.

¨   Median age for ESRF is 13 years. 

¨   Typically, edema, hematuria, and UTI are absent in NPHP.

¨   HTN is rare ( for degree of CRF ).

¨   Most children have already develop CRF when the first come to clinical attention.

¨   They have definite risk of sudden death from fluid and electrolyte imbalance (rare).

¨   If RF has not developed by the age 25, the diagnosis of rec. NPHP should be questioned.

¨   Disease recurrence has never been reported after renal transplantation.

¨   EXTRA-RENAL manifestation, occur only in recessive NPHP, but is absent from MCKD.

                                       1 – retinitis pigmentosa.

                                       2 – mental retardation.

                                       3 – skeletal changes.

                                       4 – cerebellar ataxia.

                                       5 – liver fibrosis.

                                       6 – retinal degeneration.

                                       7 – polydactyly.

¨  DIAGNOSIS:

¨   as increase serum Creatinine value in patients with nonspecific complaints.

¨   Prolonged nocturia since school age.

¨   Low early morning urine SG.

¨   Small to normal size and echogenic kidneys.

¨   Confirmed by molecular genetic diagnosis in NPHP.

¨   Ophthalmoscopy should be performed.

¨   Liver function tests and hepatic US, are important.

¨   Kidney US, or MRI. For detection of renal cysts.

¨   Kidney biopsy is not initial procedure (due to PCR).

¨  PROGNOSIS and THERAPY:

¨   There is no specific therapy.

¨   Therapy is symptomatic.

¨   Psychological counseling.

¨   Renal replacement therapy.

¨   All patients develop ESRF in first 2 decades.