It is well established that a large number of hospitalized patients present various degrees of heart and kidney dysfunction. cardiorenal syndrome (CRS), is defined as ‘disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other’.(1–3) The historical lack of clear syndrome definition and complexity of diseases contributed to a waste of precious time especially concerning diagnosis and therapeutic strategies.

The effective classification of CRS proposed in a Consensus Conference by the Acute Dialysis Quality Group essentially divides CRS into two main groups, cardiorenal and renocardiac CRS, on the basis of primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic according to disease onset. CRS type 5 (CRS-5) integrates all cardiorenal involvements induced by systemic disease.(2)

Heart failure due to myocardial infarction leading to a decreased renal arterial flow and a consequent fall in GFR finally leads to AKI OR CKD.(4) Similarly, Nonhemodynamic mechanisms have been proposed to be involved in cardiorenal syndrome including the sympathetic nervous system and renin-angiotensin aldosterone system (RAAS) activation, chronic inflammatory status and impairment of ROS/NO production.(1) Moreover, a majority of these patients develop varying levels of worsening renal function during the management of HF.(5) Patients with chronic kidney disease present various degrees of cardiovascular involvement especially due to chronic inflammatory status, volume and pressure overload, electrolyte imbalance, uncontrolled hypertension and secondary hyperparathyroidism leading to a higher incidence of calcific heart disease.(6,7)

This study sought to describe the clinical profile, outcome of cardiorenal syndrome from type 1 to type 5 in single center.

Ethical approval:

This study was approved by maharani laxmibai medical college ethical committee (4658/IEC/19/2021/SC-1) and was carried out in accordance with principles of modified declaration of Helsinki. The patients were enrolled in study after giving informed consent.

MATERIAL AND METHODS

This was single center prospective observational study of all patient who had renal dysfunction (AKI/CKD) along with heart dysfunction (acute or chronic) admitted to ICU or general ward from 1^ST April 2020 to 30^TH September 2021 in Medicine Department, Maharani Laxmibai Medical College, Jhansi. During this study 442 patient were admitted with heart failure diagnosed as per Framingham criteria and troponin t and NT-proBNP result of these, 82 patients had deranged renal function and were classified into type 1 and type 2 CRS. Similarly, 308 patients were admitted with worsening renal function, (Defined as AKI/CKD as per KDIGO guidelines) of which 27 patients were diagnosed as having heart failure which were classified as type3 and type 4 CRS. 62 patients were admitted with sepsis, of which 10 patients who had simultaneously renal and cardiac dysfunction were classified into type 5 CRS. Total of 119 patients were fulfilling inclusion criteria. Patient less than 18 years of age were excluded from this study.

Patients’ demographic details were taken. A pilot-tested questionnaire was used to collect information regarding patient’s sociodemographic profile, history of cardiovascular disease risk factors such as systemic hypertension, diabetes, dyslipidemia, history of cerebrovascular episode, hypothyroidism, and addictions in the form of alcohol, smoking, food habit and life style. Clinical examination included anthropometric measurements, recording of blood pressure and respiratory rate, assessing mental status, detailed cardiovascular, respiratory and per abdomen examination. SOFA- sequential organ failure assessment score was used to identify patients with sepsis as it facilitates simple and approximate earliest identification of sepsis outside hospitals and wards. All patients were subjected for laboratory investigations which included CBC (complete blood count), KFT (kidney function test), HBA1C, lipid profile, urine examination, trop-I, ESR, CRP, NT-proBNP /BNP, ECG, Echocardiography, Ultrasonography- KUB.

Assessment of Cardiac Function: Cardiac dysfunction was identified as patients having HF as per the Framingham criteria. 2D echocardiography (ECHO) was done to estimate left ventricular ejection fraction, diastolic dysfunction, and regional wall motion abnormality.

Assessment of Renal Function: Renal function was studied using the levels of serum creatinine and estimated glomerular filtration rate (eGFR); the latter was calculated using CKD-EPI equation and was used in staging of CKD. Ultrasonography of kidney, ureter, and bladder was done in all patients to differentiate AKI from that of CKD. The size, shape of both kidney and echogenicity of renal cortex and differentiation of the cortex and medulla were assessed.

Definition and classification of CRS: We adopted the definition suggested by Ronco et al. in 2008 at a consensus conference under the patronage of the Acute Dialysis Quality Initiative (ADQI). Cardio renal syndrome is defined as “Disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other.” CRS is classified into five types depending on whether kidney or heart was the initial organ of insult. Accordingly, in type 1 and 2 CRS, worsening of acute HF (type 1) or chronic HF (type 2) leads to kidney dysfunction. In types 3 and 4 (termed acute and chronic renocardiac syndromes, respectively), consisting of AKI or CKD causes worsening of HF. In type 5 CRS, various systemic conditions cause simultaneous worsening of the heart and kidney. (1–3)

Diabetes mellitus was defined as per guidelines of American diabetic associations.(8) Systemic hypertension diagnosed as per JNC7 criteria (Joint National Committee’s seventh report).(9) Patients who have had past documented or present history of myocardial infarction, unstable angina, percutaneous coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) were classified as having CAD.

Statistical analysis: Data was presented as either mean (SD) or proportion. To study the association of risk factors with CRS, t-test or chi-square test of significance was used. For comparison of survival and death subgroups of hospitalized patients, the nonparametric Mann-Whitney test was used. A two-way p value of less than 0.05 was considered significant. Multiple regression analysis was used to study the independent association of risk factors with outcome of cardio renal syndrome. All the analysis was done by SPSS and Microsoft excel.

RESULTS

Study included 119 patients admitted with CRS, 80 were male and 39 were female. Percentage wise male was 67.22% of total patients. Of all patients 56 (47.06%) patients were 41-60 years old, 41 were 61-80 age group. 6 were >80 years age and 16 were <40 years age.

Table 1 show that out of 119 admitted patients of CRS, type 1 was most common. 49 patients were admitted with type 1 followed by type 2 (n=33), type 4 (n=24), type 5(n=10) and type 3(n=3) respectively.

Table 1: Types of CRS and No. of patients

Out of 119 patients 67 patients from urban area and 52 patients were from rural area. Percentage wise patients from urban area were 56.30 % and from rural area 43.69%.

Table 2 shows base line characteristics of our patients. Mean eGFR was 30.34, mean LVEF was 40.84%, s. creatinine was 2.40 mg/dl, and mean HB was 11.39 g/dl, average hospital stay was 8.07 days.

Table 2: Base line characteristics of studied patients

Table 3: Symptom presentation in CRS patients

Table 3 indicated that out of 119 patients, dyspnea was most common symptom among CRS patients. 100 patients presented with dyspnea (84.03%). Most patients were in NYHA grade 3 (45 patients out of 100). 2^nd most common symptom was chest discomfort (64 patients-53.78%). 3^rd most common symptom was pedal edema (36 patients-30.25%) followed by decrease urine output (34 patients-28.57%), anasarca (14 patients-11.76%), palpitation (11 patients-9.24%), altered sensorium (7 patients-5.88%), and fever (5 patients-4.20%).

Table 4: Co-morbidities in CRS patients

Table 4 represents that in present study most common comorbidity in CRS patients was systemic hypertension. Out of 119 patients 68 patients had systemic hypertension (57.14%). 2^nd most common comorbidity in CRS was CAD. It was seen in 53 patients (44.53%). 3^rd most common was diabetes mellitus-2 (33.61%). Obesity (38 patients-31.93%), CKD (26 patients-21.84%), COPD (9 patients-7.56%), Pulmonary kochs (7 patients-5.88%) atrial fibrillation (5 patients-4.20%), hypothyroidism, RHD (each 2 patients- 1.68%), CVA, pregnancy (each 2 patients-0.84%).

Table 5: Co-morbidities and type of CRS

Table 5 shows on average CRS type 2 and 4 was associated with more co-morbidities than other types. Type 4 had average 2.58 co-morbidities while type 2 had 2.21, type 3(2), type 1 (1.97), type 5 (1.4). Type 1 had CAD more common (63.26%). Type 2 had HTN more common (63.63%). Type 3 had HTN (66.6%) and CAD (66.6%) more common. Type 4 had CKD more common (100%). Type 5 had HTN more common (50%).                    

Table 6: Risk factors in CRS

Table 6 - smoking was most common risk factor associated with CRS (56.30%). 2^nd most common risk factor was dyslipidemia (42 patients- 35.29%), 3^rd most common risk factor was sedentary life style (18 patients-15.12%). 4^th most common risk factor was alcohol (12 patients-10.08%), gutkha chewer (5 patients- 4.20%).

Table 7: Risk factors and CRS type

Table 7 Smoking was most common risk factor among type 1,2 and 4 CRS.

Table 8: Outcome in CRS

Table 8- Out of 119 patients with CRS, 21 patients died in hospital and 98 patients got discharged. Percentage and number wise most mortality seen in type 5 CRS (7 death out of 10 patients-70%) followed by type 3 CRS (1 death/3 patients-33.33%), type 2 CRS (5 death/33 patients-15.15%), type 1 CRS (6 death/49 patients- 12.24%), type 4 CRS (2 death/24 patients-8.33%).

Table 9: Number of in-hospital mortality and discharge in each type of CRS

Table 9- total of 40 patients died among patients diagnosed with CRS in total period of 6 months duration. 21 (17.65%) patients died in hospital and 98 (82.35%) patients survived. After 6-months follow-up 19 patient died out of 98 discharged patients. Out of 119 patient total of 40 patients died (33.61%). Out of 98 discharged patients 39 patients were re-admitted.

Table 10: Various parameters in Death group and Survival group

Table 10 - In this study serum creatinine, eGFR, sodium, LVEF, S. Albumin were associated with outcome in patients with CRS. They can be used for prognosticating patients with CRS.

DISCUSSION

This study done in tertiary care center of Bundelkhand region highlights the clinical, demographic and outcome profile of all types of cardiorenal syndrome.

The present study investigated 119 cases of cardiorenal syndrome (CRS) at MLB Medical College, focusing on incidence, types, outcomes, and risk factors. Findings revealed that type 1 CRS was the most common, consistent with previous studies by Prothasis et al., Shah HR et al., and Reddy et al.(10–12) These studies also reported similar patterns, with type 1 CRS leading, followed by type 2, type 4 and type 3

The study found a male predominance (67.22%), aligning with Prothasis et al. (60.42%) and Shah HR et al. (66%).(10,11) The mean age of patients (57.18 years) was slightly younger compared to Shah HR et al. (64 years) and Reddy et al. (62.87 years), suggesting regional variations in CRS demographics.

Symptomatically, dyspnoea was the most reported issue (84.03%), similar to findings by Reddy et al. (94%) and Shah HR et al. (100%). Common comorbidities included systemic hypertension (57.14%) and coronary artery disease (44.53%), mirroring Reddy et al. (74.05% hypertension) and Shah HR et al. (78% hypertension). These comorbidities highlight the need for comprehensive management of underlying conditions in CRS patients.

Regarding risk factors, smoking was the most prevalent (56.30%), higher than reports from Prothasis et al. (23.95%) and Reddy et al. (15.82%). This suggests a potentially significant regional lifestyle influence. Dyslipidaemia was also noted in 35.29%, corroborating Shah HR et al. (44%).

Mortality at discharge was 17.64%, with a rise to 33.61% within six months, consistent with Shah HR et al. (16%) and lower than Prothasis et al. (45.83%). Cardiorenal syndrome leads to higher mortality rate. In India it ranges from 6.32% to 45.83 %.(10–12)

The study noted a high readmission rate (39.79%), indicating challenges in managing CRS post-discharge, which was lower in Reddy et al. (24.68%).

Overall, this study underscores the critical need for targeted interventions and follow-up care for CRS patients, as well as further research to explore regional differences in demographics, risk factors, and outcomes. The consistent findings across various studies emphasize the importance of recognizing and addressing the complexities of cardiorenal syndrome in clinical practice.

Our study was done in single center and small size. More studies are required to assess the clinical importance of various findings in patients with CRS in the Indian subcontinent. Early diagnosis and treatment of CRS are necessary to combat the subsequent complications and achieve favorable prognosis and better patient outcome.

The study highlights the significant burden of cardiorenal syndrome (CRS) in a clinical setting, with type 1 being the most prevalent form. The demographic data suggest a predominance of male patients, particularly in the 41-60 age group, emphasizing the need for targeted screening and intervention strategies in this population.

Key symptoms and common comorbidities like systemic hypertension, coronary artery disease, and diabetes mellitus underline the multifactorial nature of CRS, necessitating a comprehensive approach to patient management.(13) The high mortality rates observed, especially in type 5 CRS, underscore the critical importance of early identification and treatment of risk factors, including lifestyle modifications.

Additionally, the study’s findings on the association between specific clinical parameters and patient outcomes provide valuable insights for prognostication. The elevated readmission rates further indicate a need for enhanced follow-up care and monitoring to improve long-term patient outcomes. Overall, this research contributes to a better understanding of CRS and reinforces the necessity for integrated healthcare strategies to address its complexities.

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